Stimulatory Effect Of Serotonin Research Articles

The role of adrenoreceptors in the implementation of the stimulatory effect of serotonin on the gastric motor activity

Purpose of the study — study of the role of adrenoreceptors in the development of the stimulatory action of serotonin on the gastric motor activity.Materials and methods. The experiments were performed on rats (27) of the Wistar line in the surgical stage of anesthesia. Electromyogram and hydrostatic pressure in the stomach cavity were recorded using a BioAmp ML132 amplifier (Adinstruments, Australia), an Maclab 8e analog-to-digital converter (Adinstruments, Australia), a Macintosh Performa 6400/180 computer, and Chart 4.2.3. program. Serotonin injected into the body to intact animals and against the background of separate and joint blockade of α- and β-adrenoreceptors.The results of the study. In experiments on rats established that the preliminary simultaneous blockade of α- and β- adrenoreceptors leads to an increase in the stimulatory effect of the stomach with the introduction of serotonin by 58%, blockade of α-adrenoreceptors only — by 62%, β-adrenoreceptor blockade — by 89%. In intact animals, the stimulatory eff ect of serotonin is only + 26%. Simultaneous blockade of α- and β-adrenoreceptors and blockade of α-adrenoreceptors only (without serotonin administration) did not aff ect the gastric motor activity of intact animals. Blockade only β-adrenoreceptors will lead to an increase in gastric contractions by 34%.Conclusion. Intact α- and β-adrenoreceptors inhibit the stimulatory eff ect of serotonin on gastric motor activity.

The effect of melanocortin (Mc3 and Mc4) antagonists on serotonin-induced food and water intake of broiler cockerels

The current study was designed to examine the effects of intracerebroventricular injections of SHU9119 [a nonselective melanocortin receptor (McR) antagonist] and MCL0020 (a selective McR antagonist) on the serotonin-induced eating and drinking responses of broiler cockerels deprived of food for 24 h (FD24). For Experiment 1, the chickens were intracerebroventricularly injected with 2.5, 5, and 10 µg serotonin. In Experiment 2, the chickens received 2 nmol SHU9119 before being injected with 10 µg serotonin. For Experiment 3, the chickens were given 10 µg serotonin after receiving 2 nmol MCL0020, and the level of food and water intake was determined 3 h post-injection. Results of this study showed that serotonin decreased food intake but increased water intake among the FD24 broiler cockerels and that these effects occurred in a dose-dependent manner. The inhibitory effect of serotonin on food intake was significantly attenuated by pretreatment with SHU9119 and MCL0020. However, the stimulatory effect of serotonin on water intake was not altered by this pretreatment. These results suggest that serotonin hypophagia and hyperdipsia were mediated by different mechanisms in the central nervous system, and that serotonin required downstream activation of McRs to promote hypophagia but not hyperdipsia in the FD24 chickens.

Functional characteristics of calcium-sensitive adenylyl cyclase of the infusorian Tetrahymena pyriformis

The calcium-sensitive forms of adenylyl cyclases (AC) have been revealed in the majority of vertebrate and invertebrate animals, as well as in several representatives of unicellular organisms, including infusoria. We have found for the first time that the AC activity in the infusorian Tetrahymena pyriformis changes in the presence of calcium ions. Calcium ions at concentrations of 0.2–20 μM stimulated the activity of this enzyme, with the maximum of the stimulatory effect being observed at 2 μM Ca2+. At a concentration of 100 μM and higher, the calcium cations inhibited the AC activity. Antagonists of calmodulin W-5 and W-7 at concentrations of 20–100 μM decreased the stimulatory effect of 5 μM Ca2+, while at the higher concentrations inhibited it completely. Another calmodulin antagonist, chloropromazine, decreased the Ca2+-stimulated AC activity only at concentrations of 200–1000 μM. The stimulatory effect of serotonin, EGF, and cAMP on AC activity was enhanced in the presence of 5 μM Ca2+. The stimulatory effect of EGF, cAMP, and insulin on AC was decreased in the presence of 100 μM Ca2+, while the effect of cAMP was also observed in the presence of calmodulin antagonists (500 μM). At the same time, stimulatory effect of D-glucose did not change in the presence of Ca2+ and calmodulin antagonists. The obtained data indicate that, in the infusorian T. pyriformis, there are calcium-sensitive forms of AC that can be stimulated by EGF, cAMP, insulin, and serotonin.

Serotonin modulates the cytokine network in the lung: involvement of prostaglandin E2

Serotonin, well known for its role in depression, has been shown to modulate immune responses. Interestingly, the plasma level of serotonin is increased in symptomatic asthmatic patients and the use of anti-depressants, known to reduce serotonin levels, provokes a decrease in asthma symptoms and an increase in pulmonary function. Thus, we tested the hypothesis that serotonin affects alveolar macrophage (AM) cytokine production, altering the cytokine network in the lung and contributing to asthma pathogenesis. AMs were treated with different concentrations of serotonin (10(-11)-10(-9) M) or 5-HT(1) and 5-HT(2) receptor agonists for 2 h prior stimulation. T helper 1 (Th1) and Th2 cytokines, prostaglandin-E(2) (PGE(2)) and nitric oxide (NO) were measured in cell-free supernatants. Serotonin significantly inhibited the production of tumour necrosis factor (TNF) and interleukin (IL)-12, whereas IL-10, NO and PGE(2) production were increased. These immunomodulatory effects of serotonin were mimicked by 5-HT(2) receptor agonist but were not abrogated by 5-HT(2) receptor antagonist, suggesting the implication of other 5-HT receptors. Inhibitors of cyclooxygenase and antibody to PGE(2) abrogated the inhibitory and stimulatory effect of serotonin on TNF and IL-10 production, respectively, whereas NO synthase inhibitor eliminated serotonin-stimulated IL-10 increase. Furthermore, PGE(2) significantly increased AM IL-10 and NO production. These results suggest that serotonin alters the cytokine network in the lung through the production of PGE(2). The reduction of Th1-type cytokine by serotonin may contribute to asthma pathogenesis.

Decrease in functional activity of G-proteins hormone-sensitive adenylate cyclase signaling system, during experimental type II diabetes mellitus

The development of experimental type II diabetes mellitus in rats was accompanied by dysfunction of inhibitory and stimulatory heterotrimeric G-proteins, components of hormone-sensitive adenylate cyclase signal system. The function of inhibitory G-proteins decreased most significantly under these conditions, which is seen from weakened regulatory effects of somatostatin (in the myocardium) and bromocriptine (in the brain striatum) realized via inhibitory G-proteins in diabetic rats compared to controls. These hormones produce less pronounced inhibitory effect on forskolin-induced activation of adenylate cyclase. In the myocardium of diabetic rats, the stimulatory effects of isoproterenol and relaxin on adenylate cyclase realized via stimulatory G-proteins were decreased to a lesser extent. In the striatum of diabetic rats the stimulatory effect of serotonin and relaxin did not differ from the control. Therefore, dysfunction of stimulatory G-proteins during type II diabetes mellitus is characterized by tissue specificity. Synthetic peptides corresponding to functionally important regions in a-subunits of G-proteins and relaxin receptor LGR7 less effectively inhibited hormone signal transduction via the adenylate cyclase system in rats with type II diabetes. These changes reflect abnormal coupling between receptors and G-proteins in tissues of diabetic rats.

Role of S2 receptors in the stimulatory effect of serotonin on hemopoietic bone marrow stem cells.

Studies by the method of splenic exocolonies with serotonin receptor blockers methysergide and cyproheptadine showed that S2 receptors are involved in the stimulatory effect of serotonin on hemopoietic bone marrow stem cells.

Effect of serotonin depletion by p-chlorophenylalanine on serum prolactin levels in estrogen-treated ovariectomized rats: insights concerning the serotoninergic, dopaminergic and opioid systems.

The stimulatory effect of serotonin on prolactin secretion is well documented, and the administration of an inhibitor of serotonin synthesis (p-chlorophenylalanine - pCPA) has the expected inhibitory action on prolactin release in most experimental situations. However, there is evidence that in certain physiological or experimental conditions, activation of the serotoninergic system can also determine inhibition of prolactin secretion. The aim of the present study was to investigate the ability of estrogen to modify the effect of pCPA on prolactin secretion and to evaluate the participation of opioid and/or dopaminergic systems in regulating pCPA-induced prolactin secretion in estradiol-treated rats. We observed that pCPA administration (200 mg/kg/day, s.c., 2 days) to ovariectomized (OVX) female rats treated with estradiol benzoate (300 microg/week for 2 weeks, or 50 microg/week for 4 weeks, s.c.) causes a significant increase in serum prolactin, whereas no effect is observed in intact rats or in OVX rats without treatment. Bromocriptine administration completely reversed prolactin values previously increased by estradiol and by pCPA [OVX rats + estradiol = 86.50 ng/ml (68.90-175.02), OVX + estradiol + pCPA = 211.30 ng/ml (142.03-311.00), OVX + estradiol + pCPA + bromocriptine = 29.35 ng/ml (23.01 - 48.74), p<0.05. Naloxone administration partially reduced estrogen-induced high prolactin concentrations, but did not affect prolactin secretion stimulation determined by pCPA. Overall, the data from this report confirm the involvement of the dopaminergic system and, to a lesser degree, of endogenous opioids in prolactin secretion stimulation determined by estradiol. Furthermore, our results suggest that the stimulatory action of pCPA on prolactin secretion in estradiol-treated OVX rats is mediated by serotonin, which may also act indirectly on dopamine neurons.

Interrelationships of GABAergic, Serotoninergic and Excitatory Amino Acid Systems in its Regulatory Effect on Prolactin Secretion in Prepubertal Rats

GABAergic, serotoninergic and excitatory amino acid systems (EAAs) regulate the prolactin (PROL) secretion in prepubertal female rats. The aim of the present paper was to determine the interrelationships of these systems on the control of this pituitary hormone. It was carried out through the following scheme: 1. The participation of the EAAs and serotonin in the effect of GABAergic system on PROL release, determined by evaluating the GABA A and GABA B receptor agonists. It was carried out on animals that were previously treated with AAEs receptor antagonist or p-chlorophenylamphetamine (PCA), this one depleting serotonin in the hypothalamus. 2. The participation of GABAergic system in the effect of serotonin and EAAs systems, determined by the evaluation of the effects of EAAs receptor agonists and of 5-HTP, a serotonin precursor. With this purpose the rats were previously treated with GABA A and GABA B receptor antagonists. 3. The interrelationships between the EAAs and the serotoninergic systems in the control of PROL secretion, determined (a) by using EAAs agonists (in rats depleted of serotonin by PCA) and (b) using EAAs antagonists (in rats treated with 5-HTP, a serotonin precursor). The administration of GABAergic agonists significantly increased PROL secretion in prepubertal female rats. Neither EAAs antagonists nor the depletion of serotonin in the brain, modified the stimulatory effects of the GABAergic system on PROL levels. This is a clear indication that the activity of the GABAergic system is independent of the serotoninergic and of the EAAs system effects on the pituitary hormone. The EAAs neurotransmitter system agonists significantly increase PROL levels. This effect was blocked by the GABAergic system antagonists but was not modified by serotonin depletion. Taking into account these facts it may be considered that the GABAergic system is involved in the stimulatory effect of EAAs on PROL secretion, this effect being independent of the serotoninergic system. 5-HTP significantly increased PROL plasma levels, and this effect was modified neither by the GABAergic nor by the EAAs receptor antagonists. These results indicate that the stimulatory effect of serotonin on PROL release is independent of the GABAergic and EAAs systems. In conclusion it may be considered that in prepubertal female rats, the GABAergic and serotoninergic systems stimulate PROL secretion by independent mechanisms that do not include EAAs. On the other hand, the effects of EAAs neurotransmission are exerted via the GABAergic system.

Serotonin directly stimulates luteinizing hormone-releasing hormone release from GT1 cells via 5-HT7 receptors.

Luteinizing hormone-releasing hormone (LHRH release, which serves as the primary drive to the hypothalamic-pituitary gonadal axis, is controlled by many neuromediators. Serotonin has been implicated in this regulation. However, it is unclear whether the central effect of serotonin on LHRH secretion is exerted directly on LHRH neurosecretory neurons or indirectly via multisynaptic pathways. The present studies were undertaken in order to examine whether LHRH secretion from immortalized LHRH cell lines is directly regulated by serotonin and, if so, to identify the receptor subtype involved. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A/7 receptor agonist, stimulated LHRH release from GT1-1 cells. This effect was blocked by ritanserin, a 5-HT2/7 receptor antagonist, but not by SDZ-216-525, a 5-HT1A antagonist. Basal LHRH release was not affected by the 5-HT2 agonist DOI. Reverse transcription and polymerase chain reaction technique (RT-PCR) was used in order to identify 5-HT1A and 5-HT7 receptor mRNA in immortalized LHRH cell lines. GT1-1 cells express mRNA for the 5-HT7, but not the 5-HT1A receptor subtypes. These results demonstrate a direct stimulatory effect of serotonin on LHRH release via 5-HT7 receptor.

Serotonin increases interleukin-6 release and decreases tumor necrosis factor release from rat adrenal zona glomerulosa cells in vitro

Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are secreted by rat adrenal zona glomerulosa cells. Serotonin increases the release of aldosterone, corti-costerone, and cortisol from the adrenal cortex. Therefore, the effects of serotonin on IL-6 and TNF release from rat adrenal zona glomerulosa cells were investigated. Cultures of rat adrenal zona glomerulosa cells were enzymatically prepared and cultured for 4-6 d. The cells were then exposed to serum-free RPMl-1640 medium containing vehicle (RPMl medium alone), serotonin, and/or endotoxin, interleukin-1β, or adrenocorticotrophic hormone (ACTH). Following a 5-h incubation, medium was removed from the cells, and IL-6 and TNF content of this medium determined with bioassays. Serotonin (1-1000 nM) increased basal IL-6 release from zona glomerulosa cells, but inhibited basal TNF release from these cells. Endotoxin and interleukin-1β (IL-1β) increased IL-6 and TNF release from zona glomerulosa cells. Serotonin potentiated IL-6 release stimulated by endotoxin and IL-1β, but inhibited TNF release stimulated by these agents. Serotonin potentiated ACTH-stimulated IL-6 release. Serotonin had no effect on IL-6 release from rat anterior pituitary cells. Because IL-6, TNF, and serotonin modify the release of aldosterone and glucocorticoids from adrenal cells, the stimulatory effects of serotonin on aldosterone and glucocorticoid release may be mediated in part by the effects of serotonin on IL-6 and TNF release from adrenal cells.

Stimulatory effects of serotonin on maturational gonadotropin release in the Atlantic croaker, Micropogonias undulatus

The effects of serotonin (5-HT) injection alone, and in combination with des Gly10 [d-Trp6]-luteinizing hormone-releasing hormone ethylamide (LHRHa), on plasma maturational gonadotropin (GtH) levels in the Atlantic croaker, Micropogonias undulatus, were examined. An injection of 5-HT (20 μg body wt) alone did not significantly elevate GtH levels, whereas simultaneous administration of LHRHa (20 ng/g body wt) and 5-HT elicited a greater elevation of plasma GtH levels than that induced by LHRHa alone. Pretreatment of 1-year-old fish with fluoxetine (10 μg/g), a 5-HT reuptake inhibitor, only slightly augmented the effect of 5-HT on GtH levels, whereas pretreatment with ketanserin (10 μg/g), a 5-HT receptor antagonist, completely inhibited the potentiating effect of 5-HT on the GtH response to LHRHa. Administration of LHRHa (20 μg/g) or 5-HT (20 μg/g) significantly elevated GtH levels in the 2- and 3-year-old croaker, but the combined treatment failed to increase GtH levels above those induced by LHRHa alone. However, with a lower dose of LHRHa (5 μg/g), the combination produced an additive effect. Serotonin (20 μg/ml media) alone, and in combination with LHRHa (10 ngiml media), significantly stimulated GtH release from the pituitaries of gonadally mature 2- and 3-year-old female croaker during an 18-hr incubation in vitro, but not from pituitaries of gonadally regressed fish. The combined treatment of LHRHa with 5-HT also significantly stimulated in vitro GtH release during 6-and 12-hr pituitary incubations, whereas these treatments alone were ineffective. The results demonstrate that a serotonergic stimulatory system for the control of GtH secretion is present in the Atlantic croaker, although preliminary results suggest that this system is only functional during certain stages of the reproductive cycle.

Serotonin-induced stimulation of cortisol secretion from human adrenocortical tissue is mediated through activation of a serotonin 4 receptor subtype

The occurrence of serotonin in the human adrenal gland was demonstrated both by immuno-histochemical and biochemical approaches. Using specific polyclonal antibodies to serotonin, the presence of numerous immunoreactive cells was revealed by means of the peroxidase-antiperoxidase technique. These cells exhibited the morphological characteristics of mast cells. Combination of high performance liquid chromatography and electrochemical detection showed the presence of substantial amounts of both serotonin and its metabolite 5-hydroxyindolacetic acid in adrenocortical extracts. The role of serotonin in the regulation of steroidogenesis from human adrenocortical slices was studied in vitro using a perifusion system technique coupled to a specific radioimmunoassay for cortisol. Graded doses of serotonin (from 10 −8M to 3 × 10 −7M) increased cortisol production in a dose-dependent manner. Prolonged exposure of adrenal fragments to serotonin (10 −7 M) induced a biphasic response, i.e. a rapid and transient increase in cortisol secretion followed by a plateau phase, suggesting the existence of a desensitization phenomenon. The stimulatory effect of serotonin (10 −7M) was not altered during infusion of the serotonin, and/or serotonin 2 receptor antagonists methysergide (10 −6 M) and ketanserin (10 −6 M), respectively. In contrast, ICS 205 930 (10 −6 M), a non-selective serotonin 3/serotonin 4 antagonist, totally abolished the response of adrenal slices to serotonin (10 t7¯ M). The benzamide derivative zacopride, considered as a serotonin 4 agonist, induced a robust stimulation of cortisol secretion. In addition, the corticotropic effects of serotonin (10 −7 M) and zacopride (10 −6 M) were not additive. Incubation of adrenocortical fragments with zacopride (10 −6 M) or serotonin (10 −6 M) caused a significant increase in cAMP formation. Taken together, these data suggest that serotonin, locally released by intra-adrenal mast-like cells, may act as a paracrine factor to stimulate cortisol secretion in man. Our results also indicate that serotonin-induced corticosteroid production is mediated through activation of a serotonin 4 receptor subtype positively coupled to adenylate cyclase.

Serotonin plays a major role in serum-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in vascular smooth muscle cells

Whole blood serum (WBS) rapidly induced the phospholipase C-mediated hydrolysis of phosphoinositides and subsequently stimulated DNA synthesis in cultured rabbit vascular smooth muscle cells (VSMCs). Ketanserin, a serotonin (S2) receptor antagonist, markedly inhibited the WBS-induced phospholipase C reaction and DNA synthesis. Serotonin by itself had a weak mitogenic activity for VSMCs, but this vasoconstrictor markedly stimulated the platelet-derived growth factor- and epidermal growth factor-induced DNA synthesis. The stimulatory effect of serotonin on the growth factor-induced DNA synthesis was inhibited by ketanserin. The amount of serotonin contained in WBS was sufficient to induce the phospholipase C reaction and stimulate the growth factor-induced DNA synthesis. These results indicate that serotonin plays a major role in the WBS-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in rabbit VSMCs and suggest that serotonin may act as an important growth regulator for VSMCs in addition to acting as a vasoconstrictor.

P-121 - Stimulatory effects of serotonin on both ANP-sensitive membrane-associated and cytosolic guanylate cyclases in NG108-15 cells

P-121 - Stimulatory effects of serotonin on both ANP-sensitive membrane-associated and cytosolic guanylate cyclases in NG108-15 cells

Participation of serotonin and substance P in the action of cholecystokinin on colonic motility

Cholecystokinin (CCK) has a potent stimulatory effect on gastrointestinal motility. The mechanism of CCK-generated contractions in the colon is unknown. We explored the possibility that CCK-mediated contractions in the guinea pig colon occur via a serotonin and/or substance P pathway. In the circular layer, octapeptide of CCK (CCK-8) had no effect under basal conditions, but after treatment with tetrodotoxin the peptide generated dose-dependent contractions (ED50 6 X 10(-8) M). In the longitudinal layer, CCK-8 produced dose-related contractions (ED50 6 X 10(-9) M) blocked by tetrodotoxin and markedly inhibited by the substance P antagonist, Spantide. The effect of substance P was not significantly antagonized by tetrodotoxin but was markedly attenuated by Spantide. Serotonin produced dose-dependent contractions in the longitudinal layer (ED50 4 X 10(-8) M). Desensitization to serotonin antagonized the action of CCK-8 but had no effect on substance P-mediated contractions. Pretreatment with the serotonin antagonist mianserin inhibited CCK-8- but not substance P-generated contractions. In contrast, the stimulatory effect of serotonin was antagonized by Spantide. These studies suggest that in the circular layer of the guinea pig colon CCK-8 has no effect under basal conditions, but after removal of tonic inhibition, the peptide produced a direct stimulatory effect. In contrast, CCK-8 generated contractions in guinea pig colon longitudinal layer, mediated by a pathway involving serotonin and substance P.

Stimulation of aortic smooth muscle cell mitogenesis by serotonin.

Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 microM serotonin with increased incorporation of [3H]thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 microM. At a concentration of 1 microM, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was approximately 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine were inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors.

Effect of serotonin on bethanechol-stimulated gastric acid secretion and gastric antral motility in dogs.

The purpose of the present study was to evaluate the effect of serotonin on bethanechol-stimulated gastric acid secretion and antral motility in conscious dogs with gastric fistula. Bethanechol stimulated the acid secretion dose-dependently and maintained the frequency and strength of the antral contractions at a high level. Serotonin inhibited the acid secretion dose-dependently, whereas the antral motility was stimulated. The acid inhibition was blocked by propranolol, and dose-response analysis showed inhibition of a non-competitive type. This study thereby shows that serotonin inhibits bethanechol-stimulated gastric acid secretion similarly to salmefamol (beta 2-adrenergic agonist)--that is, dose-dependently and non-competitively. Serotonin has been proposed to be a mediator of the beta-adrenergic influence on gastric function in vivo, but the counteracting effect of propranolol and the stimulatory effect of serotonin on motility contradict this hypothesis.

Evidence that serotonergic neurons in the dorsal raphe nucleus exert a stimulatory effect on the secretion of renin but not of corticosterone

Data from previous experiments in rats indicate that release of serotonin in the central nervous system increases renin and corticosterone secretion 32. To determine which serotonergic neurons are involved, lesions of the dorsal or median raphe nuclei were produced by local injections of 5,7-dihydroxytryptamine (5,7-DHT) in rats, and 2 weeks later, the renin responses to parachloroamphetamine (PCA) were determined. Plasma corticosterone was also measured. PCA produced significant increases in plasma renin activity and plasma corticosterone in sham-lesioned animals and animals with median raphe lesions. The plasma corticosterone response to PCA was also normal in rats with dorsal raphe lesions but the renin response was significantly reduced. The data support the hypothesis that serotonergic neurons in the dorsal raphe nucleus are part of a neural pathway mediating increased renin secretion, and that the stimulatory effect of serotonin on corticosterone secretion is mediated by a different pathway.

Serotonin stimulates adenosine 3',5'-monophosphate accumulation in parathyroid adenoma.

The effect of serotonin on cAMP accumulation in parathyroid adenoma tissue from patients with primary hyperparathyroidism was studied in vitro. Incubation with 10(-5) M serotonin elicited a marked increase (of 90--150%) in cAMP content in slices of parathyroid adenoma tissue. This stimulatory effect of serotonin was already apparent after 2 min of incubation; stimulation by serotonin was dose dependent, with the highest stimulation being achieved at 10(-4) M serotonin. The serotonin antagonists, methylsergide and cinanserin, in concentrations equimolar to serotonin completely blocked the stimulatory effect of serotonin on cAMP increase. The serotonin content in surgically removed parathyroid adenoma tissue, as determined by fluorometric assay, was 6.4 +/- 1.2 pmol/mg wet wt (approximately 0.8 x 10(-5) M). The present observations demonstrate that parathyroid adenoma tissue has a high content of serotonin, and serotonin stimulates cAMP accumulation in this tissue. Since cAMP acts as a mediator of parathyroid hormone (PTH) release, our results suggest that serotonin could be one of the factors regulating PTH secretion and/or contributing to PTH hypersecretion in various forms of primary hyperparathyroidism.

Effects of serotonin on iodide and intermediary metabolism in isolated thyroid cells.

Serotonin in concentrations of 1 and 10 μg/ml greatly stimulated the organification of iodine and the formation of iodothyronines in suspensions of isolated thyroid cells. Iproniazid enhanced the stimulatory action of low, but not of high, concentrations of serotonin. The effects of serotonin on the iodine metabolism of isolated cells were blocked by phentolamine, but not by either propranolol or reducing agents (ascorbate, sodium bisulfite). Serotonin also stimulated the conversion of glucose-l-14C to 14CO2, the incorporation of 14C-labeled amino acids into TCA-precipitable proteins by isolated cells. In addition, adenyl cyclase activity was stimulated by serotonin in both intact and sonicated preparations of isolated cells. The precursors of serotonin, L-tryptophan and 5-hydroxytryptophan, as well as its metabolite, 5-hydroxyindolacetic acid, did not stimulate either iodine metabolism or adenyl cyclase activity, while tryptamine did. These findings suggest that the stimulatory effect of serotonin depend...