Maintenance Of Body Fluid Homeostasis Research Articles

Cellular Senescence as a Brake or Accelerator for Oncogenic Transformation and Role in Lymphatic Metastasis.

Cellular senescence-the irreversible cell cycle arrest driven by a variety of mechanisms and, more specifically, the senescence-associated secretory phenotype (SASP)-is an important area of research in the context of different age-related diseases, such as cardiovascular disease and cancer. SASP factors play both beneficial and detrimental roles in age-related disease progression depending on the source of the SASPs, the target cells, and the microenvironment. The impact of senescence and the SASP on different cell types, the immune system, and the vascular system has been widely discussed. However, the impact of replicative or stress-induced senescence on lymphatic biology and pathological lymphangiogenesis remains underexplored. The lymphatic system plays a crucial role in the maintenance of body fluid homeostasis and immune surveillance. The perturbation of lymphatic function can hamper normal physiological function. Natural aging or stress-induced premature aging influences the lymphatic vessel structure and function, which significantly affect the role of lymphatics in tumor dissemination and metastasis. In this review, we focus on the role of senescence on lymphatic pathobiology, its impact on cancer, and potential therapeutic interventions to manipulate the aged or senescent lymphatic system for disease management.

A‐Kinase anchoring protein 2 (AKAP2) and Pendrin; cross‐talk between cell signaling and renal physiology

Kidney tubules play a pivotal role in the maintenance of body fluid homeostasis and pH regulation. Accordingly, kidney disorders are known to be strongly associated with hypertension and acid‐base imbalance. In the kidney, the intercalated cells of the nephron are the main site of acid‐base balance: type A are acid‐secreting whereas type B are base‐secreting. The chloride bicarbonate exchanger Pendrin is present in type B intercalated cells and participates actively in regulating blood pressure and NaCl balance. It is still not entirely deciphered how Pendrin activity is regulated; nevertheless, it was previously demonstrated that Pendrin is regulated by c‐AMP/Protein Kinase A (PKA) signaling pathway. Consequently, in this study, our hypothesis is that the A‐Kinase anchoring protein 2 (AKAP2), strongly expressed in the kidney, regulates in time and space the intracellular signal transduction.In order to investigate AKAP2 involvement in Pendrin regulation and trafficking to the apical plasma membrane, we generated an inducible and nephron‐specific Akap2Pax8/LC1 mice knockout model. By confocal microscopy, fluorescent immunostaining on kidney tissue sections showed that AKAP2 is present in the tubules and most importantly colocalizes with Pendrin at the apical plasma membrane of the intercalated cells. To show that Pendrin and AKAP2 are interacting, we used the Proximity Ligation Assay (PLA) and, positively, we could reveal the association between the two proteins. The latter finding was also confirmed in vitro taking advantage of the Opossum Kidney Cell line (OKP) stably expressing Pendrin and co‐transfected with AKAP2, we could co‐immunoprecipitate Pendrin and AKAP2 after crosslinking on live cells. Fluorescent immunostaining in Akap2Pax8/LC1 show that Pendrin tends to be shifted from the apical membrane (seen in control mice) to intracellular compartments.In conclusion, our data suggest that AKAP2 and Pendrin are interacting, and AKAP2 may play a key role in Pendrin trafficking to the apical plasma membrane, hence in regulating its activity.

Thirst recruits phasic dopamine signaling through subfornical organ neurons

Thirst is a highly potent drive that motivates organisms to seek out and consume balance-restoring stimuli. The detection of dehydration is well understood and involves signals of peripheral origin and the sampling of internal milieu by first order homeostatic neurons within the lamina terminalis-particularly glutamatergic neurons of the subfornical organ expressing CaMKIIa (SFOCaMKIIa). However, it remains unknown whether mesolimbic dopamine pathways that are critical for motivation and reinforcement integrate information from these "early" dehydration signals. We used in vivo fiber photometry in the ventral tegmental area and measured phasic dopamine responses to a water-predictive cue. Thirst, but not hunger, potentiated the phasic dopamine response to the water cue. In euvolemic rats, the dipsogenic hormone angiotensin II, but not the orexigenic hormone ghrelin, potentiated the dopamine response similarly to that observed in water-deprived rats. Chemogenetic manipulations of SFOCaMKIIa revealed bidirectional control of phasic dopamine signaling during cued water reward. Taking advantage of within-subject designs, we found predictive relationships between changes in cue-evoked dopamine response and changes in behavioral responses-supporting a role for dopamine in motivation induced by homeostatic need. Collectively, we reveal a putative mechanism for the invigoration of goal-directed behavior: internal milieu communicates to first order, need state-selective circuits to potentiate the mesolimbic dopamine system's response to cues predictive of restorative stimuli.

Effects of Oryeongsan in 2K1C rats through regulation of renin‐angiotensin‐aldosterone system and ANP system

Oryeongsan (ORS) which was first recorded in SangHanLoon, the classic of traditional Chinese medicine describing treatments of disordered body fluid balance. Renal hypertension is caused by renovascular dysfunction through an activation of renin‐angiotensin‐aldosterone system (RAS). The RAS is one of the most important regulators in maintenance of body fluid homeostasis and in long‐term regulation of blood pressure. The purpose of this study is to identify effects of ORS on regulation of renal function, change of blood pressure and RAS in the two‐kidney one‐clip (2K1C) renal hypertensive rats. Experiments were performed in four experimental groups: sham rats, 100 mg/kg/day ORS in sham rats, 2K1C rats and ORS in 2K1C rats, respectively. After 4 weeks of operation, sham and 2K1C rats were administered with vehicle or ORS for 3 weeks. Urinary volume, urinary excretion of Na+, K+, Cl−, osmolality and creatinine were measured. The 2K1C rats showed significantly higher systolic blood pressure (SBP) compared with sham rats. ORS treatment for 3 weeks markedly decreased the SBP in 2K1C rats. ORS significantly increased urinary volume, urinary excretion of electrolytes, and clearance of creatinine (CCr) in 2K1C rats. ORS significantly suppressed plasma level of PRA, Angiotensin II and aldosterone in 2K1C rats. Also, ORS suppressed the upregulated RAS components in the kidney from 2K1C rats. However, ORS increased plasma level of ANP in 2K1C rats. These findings suggest that ORS may elicit renal and vascular effects via two ways: directly and indirectly through activation of the ANP system and inhibition of the RAS.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The role of estradiol in adrenal insufficiency and its interaction with corticosterone on hydromineral balance

Estradiol (E2) plays an important role in controlling the homeostasis of body fluids. Several studies have reported the involvement of the hypothalamic pituitary adrenal axis (HPA) in the homeostatic control of hydromineral balance and the influence of estrogens on the modulation of this system. Nevertheless, until now, the physiological relevance of HPA axis activity on the hydromineral balance in females has not yet been fully elucidated. Therefore, the objective of the present study was to evaluate the effects of E2 (20μg/animal) pretreatment on neuroendocrine and hydroelectrolyte changes induced by adrenalectomy (ADX) with or without glucocorticoid hormone replacement (corticosterone, CORT; 10mg/kg) in ovariectomized rats (OVX). The results show that sodium appetite, natriuresis and the elevated plasma angiotensin II (ANG II) concentration induced by ADX were attenuated by E2 pretreatment. Additionally, a reduction of AT1 mRNA expression in the subfornical organ (SFO) and an increase in plasma atrial natriuretic peptide (ANP) concentrations by E2 pretreatment were observed. E2 pretreatment reversed the reduction in water intake induced by ADX in ADX CORT-replaced rats. Moreover, E2 pretreatment attenuated corticotropin releasing factor (CRF) mRNA expression in the paraventricular nucleus (PVN) induced by ADX. In contrast, E2 pretreatment increased CRF mRNA expression in the PVN in ADX CORT-replaced rats. Taken together, these results suggest that E2 has an important role in the modulation of behavioral and neuroendocrine responses involved in the maintenance of body fluid homeostasis in ADX rats with or without glucocorticoid replacement therapy.

Sensory circumventricular organs in health and disease

Circumventricular organs (CVOs) are specialized brain structures located around the third and fourth ventricles. They differ from the rest of the brain parenchyma in that they are highly vascularised areas that lack a blood-brain barrier. These neurohaemal organs are classified as "sensory", when they contain neurons that can receive chemical inputs from the bloodstream. This review focuses on the sensory CVOs to describe their unique structure, and their functional roles in the maintenance of body fluid homeostasis and cardiovascular regulation, and in the generation of central acute immune and febrile responses. In doing so, the main neural connections to visceral regulatory centres such as the hypothalamus, the medulla oblongata and the endocrine hypothalamic-pituitary axis, as well as some of the relevant chemical substances involved, are described. The CVOs are vulnerable to circulating pathogens and can be portals for their entry in the brain. This review highlights recent investigations that show that the CVOs and related structures are involved in pathological conditions such as sepsis, stress, trypanosomiasis, autoimmune encephalitis, systemic amyloidosis and prion infections, while detailed information on their role in other neurodegenerative diseases such as Alzheimer's disease or multiple sclerosis is lacking. It is concluded that studies of the CVOs and related structures may help in the early diagnosis and treatment of such disorders.

The glomerulus – a view from the inside – the endothelial cell

The glomerular endothelial cells are unique both in location and anatomy compared to most other endothelial cells throughout the body. The absence of a diaphragm with retention of a basement membrane and fenestrations enable these uniquely situated cells to have a key role in filtration performed by the kidney. Interaction with other glomerular cells such as the podocytes and mesangial cells, as well as with circulating and infiltrating inflammatory cells, contribute to the final impact of the glomerular endothelial cells on maintenance of body fluid homeostasis and modulation of disease. Thus, endothelial cells contribute to hemodynamic function, reactive oxygen stress, regulate the balance between pro-thrombotic and anti-thrombotic forces, and importantly, contribute to fibrosis, the key injury of progressive chronic kidney disease. Repair of endothelial cell damage and restoration of segmentally sclerosed glomeruli are key areas considered for intervention in chronic kidney disease. This review will focus on the structure, function, and interplay of endothelial cells with other glomerular cells and systemic factors, their impact on renal disease and give rationale for possible intervention that may forestall progressive injuries.

Central cholinergic signal-mediated neuroendocrine regulation of vasopressin and oxytocin in ovine fetuses

BackgroundThe hypothalamic-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP) and oxytocin (OT) in response to a variety of signals, including osmotic and nonosmotic stimuli. It is well established that central cholinergic mechanisms are critical in the regulation of cardiovascular responses and maintenance of body fluid homeostasis in adults. Our recent study demonstrated that intracerebroventricular (i.c.v.) injection of carbachol elicited an increase of blood pressure in the near-term ovine fetuses. However, in utero development of brain cholinergic mechanisms in the regulation of the hypothalamic neuropeptides is largely unknown. This study investigated AVP and OT neural activation in the fetal hypothalamus induced by central carbachol.ResultsChronically prepared near-term ovine fetuses (0.9 gestation) received an i.c.v. carbachol (3 μg/kg). Fetal blood samples were collected for AVP and OT assay, and brains were used for c-fos mapping studies. I.c.v. carbachol significantly increased fetal plasma AVP and OT concentrations. Intense FOS immunoreactivity (FOS-ir) was observed in the fetal supraoptic nuclei (SON) and paraventricular nuclei (PVN) in the hypothalamus. Double labeling demonstrated that a number of AVP- and OT-containing neurons in the fetal SON and PVN were expressing c-fos in response to central carbachol.ConclusionThe results indicate that the central cholinergic mechanism is established and functional in the regulation of the hypothalamic neuropeptides during the final trimester of pregnancy. This provides evidence for a functional link between the development of central cholinergic mechanisms and hypothalamic neuropeptide systems in the fetus.

Jacques Benoit Lecture: The Neuroendocrine View of the Angiotensin and Apelin Systems

The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III display the same affinity for type 1 and type 2 Ang II receptors. Both peptides, injected intracerebroventricularly, similarly increase arginine vasopressin (AVP) release and blood pressure (BP); however, because Ang II is converted in vivo to Ang III, the identity of the true effector is unknown. We review new insights into the predominant role of brain Ang III in the control of BP, underlining the fact that brain aminopeptidase A (APA), the enzyme generating brain Ang III, may therefore be an interesting candidate target for the treatment of hypertension. This justifies the development of potent systemically active APA inhibitors, such as RB150, as prototypes of a new class of antihypertensive agents for the treatment of certain forms of hypertension. We also searched for a putative angiotensin receptor subtype specific for Ang III and isolated a seven transmembrane-domain G protein-coupled receptor corresponding to the receptor for apelin, a newly-discovered peptide isolated from bovine stomach. Apelin and its receptor are expressed in magnocellular vasopressinergic neurones in the hypothalamus. The central injection of apelin in lactating rats decreases the phasic electrical activity of vasopressinergic neurones and the systemic secretion of AVP, inducing water diuresis. Apelin is therefore a natural inhibitor of the antidiuretic effect of AVP. In addition, systemic administration of apelin decreases BP, improves cardiac contractility and reduces cardiac loading. The development of nonpeptide agonists of the apelin receptor may provide new therapeutic tools for treating water retention, hyponatraemia and cardiovascular diseases. Angiotensins and apelin thus exert opposing but complementary effects, and are thereby determinant for the maintenance of body fluid homeostasis and cardiovascular functions.

Distribution of c-Fos immunoreactive neurons in the brain after intraperitoneal injection of apelin-12 in Wistar rats

The present study surveyed activation of central neurons following peripheral administration of apelin-12 (AP12), an apelin peptide homologue, by examining the distribution of neurons expressing c-Fos protein. AP12 is known to induce gastric acid secretion among other physiological functions such as regulation of circulation. It was recently reported that apelin counteracted the effect of arginine vasopressin (AVP) in the maintenance of body fluid homeostasis. We attempted to clarify which neurons in the central nervous system express c-Fos protein after intraperitoneal injection of AP12. Intraperitoneally administered AP12 induced expression of c-Fos protein in several nuclei throughout the brain. In the paraventricular nucleus of the hypothalamus (PAH), lateral hypothalamic area (LH), paraventricular nucleus of the thalamus (PVT), periaqueductal gray matter (PAG), bed nucleus of the stria terminalis (BNST), locus coeruleus (LC), lateral parabrachial nucleus (Pbl), the complex of the solitary tract nucleus (NTS) and dorsal motor nucleus of the vagus nerve (DMX), numbers of neurons expressing c-Fos protein were much higher in test than in control experiments. These findings suggest that AP12 stimulates central neurons that may play roles in the regulation of gastric acid, and hypothalamic neurons that may play roles in the maintenance of body fluid homeostasis as well as other physiological functions.

AJP: Regulatory, Integrative and Comparative Physiology: 2007 and beyond

“ in·te·gra·tive, adj., serving to form, coordinate, or blend into a functioning or unified whole ([1][1]).” this single term best describes, in my eyes, the main theme of our journal. I am pleased to introduce to you, the readers of AJP: Regulatory, Integrative and Comparative Physiology ,

Polybrominated Diphenyl Ethers and ortho-Substituted Polychlorinated Biphenyls as Neuroendocrine Disruptors of Vasopressin Release: Effects during Physiological Activation In Vitro and Structure-Activity Relationships

The neuropeptide, vasopressin (VP) is synthesized in magnocellular neuroendocrine cells (MNCs) located within the supraoptic (SON) and paraventricular (PVN) nuclei of the mammalian hypothalamus. VP has multiple functions including maintenance of body fluid homeostasis, cardiovascular control, learning and memory, and nervous system development. Polybrominated diphenyl ethers (PBDEs), used as additive flame retardants, have been shown to interfere with hormone metabolism and function. Previously, we demonstrated that the technical polychlorinated biphenyl (PCB) mixture, Aroclor 1254, inhibits somatodendritic VP release from the SON of osmotically stimulated rats. The objectives of the current study were to test whether PBDEs affect central VP release in a similar manner and to determine the potency of several PCB and PBDE congeners in order to identify a common mode of action for these persistent chemicals. The current work shows that the commercial PBDE mixture (DE-71) significantly decreased somatodendritic VP release from rat SON punches in a strain-independent manner. In addition, the specific congeners PBDE 47 and PCB 47 (15 and 5 microM) were also neuroactive in this system. To explore structure/activity relationships, we compared the effects of PBDE 77 with PCB 77. PBDE 77, but not PCB 77 significantly reduced VP release. These results show that like PCBs, PBDEs perturb signaling mechanisms responsible for hormone release, and that environmentally relevant PBDE congeners are more neuroactive than the commercial mixtures with noncoplanarity of these compounds playing a role in promoting neuroactivity.

L’apéline, un inhibiteur naturel de l’effet antidiurétique de la vasopressine

Apelin is a peptide that was recently isolated as the endogenous ligand for the human orphan APJ receptor, a G protein-coupled receptor which shares 31 % amino-acid sequence identity with the angiotensin type 1 receptor. Apelin naturally occurs in the brain and plasma as 13 (pE13F) and 17 amino-acid (K17F) fragments of a single pro-peptide precursor. In transfected CHO cells, K17F and pE13F bind with high affinity to the rat APJ receptor, promote receptor internalization, and inhibit forskolin-induced cAMP formation. In the same cells, pE13F activates MAP kinase and PI3 kinase pathways. Apelin and APJ receptors are both widely distributed in the brain but are particularly highly expressed in the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei. Dual labeling studies demonstrate that within these two nuclei, apelin and its receptor are colocalized with vasopressin (AVP) in a subset of magnocellular neurons. In lactating rats, characterized by increases in both synthesis and release of AVP, central injection of apelin inhibits the phasic electrical activity of AVP neurons, reduces plasma AVP levels, and increases aqueous diuresis. Moreover, water deprivation, while increasing the activity of AVP neurons, reduces plasma apelin concentrations and induces an intra-neuronal pile up of the peptide, thereby decreasing the inhibitory effect of apelin on AVP release and preventing additional water loss at the kidney level. Taken together, these data demonstrate that apelin counteracts the effects of AVP in the maintenance of body fluid homeostasis. In addition, apelin and its receptor are present in the cardiovascular system, i.e. heart, kidney and vessels. Systemically administered apelin reduces arterial blood pressure, increases cardiac contractility and reduces cardiac loading. The development of non peptidic analogs of apelin may therefore offer new therapeutic avenues for the treatment of cardiovascular disorders.

Neuroendocrine control of body fluid metabolism.

Mammals control the volume and osmolality of their body fluids from stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+ receptors and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrated response, which depends on the integrity of the anteroventral region of the third ventricle, e.g., organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. The hypothalamo-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and nonosmotic stimuli. Since the discovery of the atrial natriuretic peptide (ANP), a large number of publications have demonstrated that this peptide provides a potent defense mechanism against volume overload in mammals, including humans. ANP is mostly localized in the heart, but ANP and its receptor are also found in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation. Blood volume expansion acts not only directly on the heart, by stretch of atrial myocytes to increase the release of ANP, but also on the brain ANPergic neurons through afferent inputs from baroreceptors. Angiotensin II also plays an important role in the regulation of body fluids, being a potent inducer of thirst and, in general, antagonizes the actions of ANP. This review emphasizes the role played by brain ANP and its interaction with neurohypophysial hormones in the control of body fluid homeostasis.

Molecular diversity of organic cation transporter (OCT) mediating renal excretion of drugs

Tubular absorption and urinary secretion are important physiological functions for the maintenance of body fluid homeostasis and detoxification of drugs and xenobiotics. The proximal tubular epithelial cells play a principal role in limiting or preventing the toxicity of administered drugs by actively secreting organic cations from the circulation into the urine. Rat (r) OCT2 was identified as a second member of the organic cation transporter (OCT) family and is predominantly expressed in the kidney. In the reverse-transcriptase-polymerase chain reaction of microdissected nephron segments, rOCT1 mRNA was detected primarily in the superficial and juxtamedullary proximal convoluted tubules, whereas rOCT2 mRNA was detected widely in the superficial and juxtamedullary proximal straight tubules and some other nephron segments. The inhibitory potencies of cationic drugs and endogenous cations on the tetraethylammoniun (TEA) uptake via rOCT1 and rOCT2 indicates that rOCT1 and rOCT2 have similar affinity for many compounds, although there are moderate differences in the affinity for several compounds, such as 1-methyl-4-phenyl-pyridinium, dopamine, disopyramide, and chlorpheniramine. On the other hand, there were gender differences in the expression levels of rOCT2, but not of rOCT1, in rat kidneys; both mRNA and protein levels of rOCT2 in the kidneys were higher in males than females. These results suggest that rOCT1 and rOCT2 play distinct roles in the basolateral membranes of renal tubules mediating tubular secretion of cationic drugs.

Polyethylene glycol-induced hypovolemia affects the expression of MCH mRNA, but not dynorphin or secretogranin II mRNAs, in the rat lateral hypothalamus

Two prominent neuron populations of the rat lateral hypothalamus express genes encoding respectively the prepromelanin-concentrating hormone (MCH) or dynorphin (DYN) and secretogranin II (SGII). Their roles remain hypothetical in mammals. In the present study, we examined the changes in MCH, DYN and SGII gene expression in dehydrated rats compared to controls. Dehydration was obtained by subcutaneous injection of polyethylene glycol (PEG) resulting in a large reduction of the extracellular fluid volume. Using competitive semi-quantitative RT-PCR and in situ hybridization methods, PEG-injected animals showed a significant increase of MCH mRNA level but no variation of DYN and SGII mRNA levels. These results confirm previous observations suggesting that intra- and extracellular dehydration challenges affect different regulation circuits; they indicate that both neuron populations could be involved in the maintenance of body fluid homeostasis, directly, or indirectly, as integrators of various information leading to goal-oriented behaviour.

Role of interleukin 1β in the integrative mechanisms and the maintenance of body fluid homeostasis in conscious rats

Changes in the central ANF-system of renovascular hypertensive rats. The central atrial natriuretic peptides (ANF)-system was investigated in volume-dependent one-kidney, one-clip (1K1C) and renin-dependent two-kidney, one-clip (2K1C) renovascular hypertensive rats by radio-immunological measurement of ANF concentration in 18 selected brain areas. Significant changes were found in nine brain areas of 1K1C and in eight brain areas of 2K1C hypertensive rats. Except unidirectional changes in the organum vasculosum laminae terminalis and the supraoptic nucleus, ANF concentration was changed in the opposite direction in all other brain areas, with an activation of the central ANF system in 1K1C and an inhibition in 2K1C hypertension. The localization of the alterations (circumventricular organs, anteroventral third ventricle region, hypothalamo hypophyseal system, brain stem) implies major differences in the central regulation of blood pressure and electrolyte and fluid homeostasis between these two models. The activation of the central ANF system in 1K1C hypertension may be a compensatory mechanism to prevent further increments in blood pressure and plasma volume. In contrast, the depression of the central ANF system in 2K1C hypertension may promote the elevation of the blood pressure.

Sensory circumventricular organs and brain homeostatic pathways.

Circumventricular organs (CVOs), small structures bordering the ventricular spaces in the midline of the brain, have common morphological and endocrine-like characteristics that distinguish them from the rest of the nervous system. Among their unique features are cellular contacts with two fluid phases--blood and cerebrospinal fluid--and neural connections with strategic nuclei establishing circuitry for communications throughout the neuraxis. A variety of additional morphological and functional characteristics of the CVOs implicates this group of structures in a wide array of homeostatic processes. For three of the circumventricular organs--the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT), and the area postrema (AP)--recent findings demonstrate these structures as targets for blood-borne information reaching the brain. We propose that these three sensory CVOs interact with other nuclei in the maintenance of several homeostatic processes by way of neural and humoral links. We emphasize the collective role of brain CVOs in the maintenance of body fluid homeostasis as a model for the functional integration of these fascinating "windows of the brain" within central neurohumoral systems.

Role of the “little brain” in the gut in water and electrolyte homeostasis 1

The enteric nervous system plays a key role in maintenance of body fluid homeostasis by regulating the transport of ions by the intestinal epithelium. The epithelial cells normally absorb large volumes of fluid and ions daily, but tonically active submucosal neurons continuously suppress ion transport and limit the absorptive capacity of the intestine. Specialized nerve endings detect chemical, osmotic, or thermal alterations of the luminal contents or mechanical activity of the gut wall and encode this information as action potentials that propagate along nerve processes to the ganglia. Information transfer within the ganglia occurs at nicotinic cholinergic or other synapses. Ion transport is altered when neurotransmitters released from motor neurons interact with receptors on epithelial cells to initiate stimulus-response coupling. The signals that transduce changes in epithelial ion transport are largely unknown, except for acetylcholine, but may include vasoactive intestinal peptide or other peptides. These trigger changes in intracellular messengers that influence the state of ionic channels in the epithelial cells and thereby inhibit absorptive processes or stimulate secretory mechanisms. When conservation of salt and water is necessary, command signals from the central nervous system, and perhaps from the myenteric ganglia, will shut down the synaptic circuits in the submucosal ganglia and enhance the absorptive capacity of the bowel.

The supraoptic nucleus: Afferents from areas involved in control of body fluid homeostasis

Physiological evidence indicates that the supraoptic nucleus may be an important integrating region for information relating to body fluid homeostasis. It is known that the supraoptic nucleus receives neural influences from brain receptive zones for plasma osmolality and angiotensin II, as well as from relay centers for blood pressure and blood volume. It is also known that these influences interact to modulate vasopressin release from the supraoptic nucleus. Therefore, a detailed investigation of the neurochemical afferents to the supraoptic nucleus from regions of the lamina terminalis and the brainstem was undertaken. Injection of a fluorescent retrograde tracer, doxorubicin, into the supraoptic nucleus was combined with histochemistry of angiotensin II and catecholamines. Following supraoptic nucleus injection, retrograde label was found in forebrain neurons of the subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminals. Some labeled cells in the subfornical organ and organum vasculosum of the lamina terminalis were also found to contain angiotensin II immunoreactivity. In the brainstem, retrograde label was found in neurons of the A1, A2 and A6 cell groups. Many of these cells were also found to contain catecholamine fluorescence or tyrosine hydroxylase immunoreactivity. Corroboration of the A2 projection was obtained by lesions of this nucleus, which reduced catecholamine fluorescence in the supraoptic nucleus. These findings provide an anatomical basis for the functional observations that the supraoptic nucleus plays a key integrative role in the maintenance of body fluid homeostasis.