Vasoactive Intestinal Peptide Secretion Research Articles

Role of VIP in the regulation of LH secretion in the female rat

Vasoactive intestinal peptide (VIP) is found within neurons throughout the body. It influences the secretion of several hormones of the anterior pituitary by neural and pituitary actions. We review work from our laboratory that indicates that VIP inhibits the secretion of luteinizing hormone (LH) by a hypothalamic action. Experiments involving neural lesions indicate that VIP acts on the receptor field in the paraventricular nuclei of neurons whose cell bodies are located in the suprachiasmatic nuclei. The effect on LH secretion is subsequently mediated by a nonVIPergic pathway, which does not appear to involve either dopamine or endogenous opioids. Experiments with the specific VIP antagonist, [4Cl- D-Phe 6,Leu 17]VIP, indicate that the actions on LH secretion of VIP and of the related peptides, growth hormone-releasing hormone and secretin, are mediated by VIP-preferring receptors. VIP also blocks the steroid-induced LH surge in the ovariectomized rat. The VIP antagonist induces a significant, but small increase in LH secretion in the intact rat, indicating that VIP has a modulatory, rather than deterministic, role in the regulation of LH secretion.

Growth hormone releasing factor and vasoactive intestinal peptide stimulate rat granulosa cell plasminogen activator activity in vitro during follicular development

Growth hormone-releasing factor (GRF) and vasoactive intestinal peptide (VIP) are two structurally homologous peptides sharing common target cell receptor and known to enhance FSH-induced steroidogenesis of undifferentiated granulosa cell in vitro. Although VIP, has been reported to stimulate plasminogen activator (PA) activity in rat granulosa cells, our knowledge on the actions and interactions of these two peptides with FSH in the regulation of rat granulosa cell PA system during follicular development remains incomplete. Undifferentiated and differentiated rat granulosa cells from pre-antral (DES-treated rats) and antral (eCG-treated rats) follicles, respectively, were cultured in a chemically defined medium in the absence and presence of FSH (400 ng/ml), GRF (10 −8–10 −5 M) and/or VIP (10 −9–10 −5 M). Net secreted (PAs) and cell-associated (PAc) PA activities was measured by the fibrinolysis assay and characterized by the fibrin overlay method. Granulosa cell differentiative (progestin secretion) and proliferative (DNA synthesis) responses were analyzed by radioimmunoassay and [ 3H]thymidine incorporation, respectively. Both GRF and VIP stimulated PAs and PAc activities in a concentration-dependent manner in 24-h cultures of granulosa cells from the two stages of follicular development. They (10 −5 M) enhanced FSH-stimulated PAs activity in granulosa cell cultures of pre-antral follicles, with GRF being more effective than VIP. On the contrary, only GRF (10 μM) potentiated FSH-induced PAs and PAc activities in cultures of granulosa cell from antral follicles. The stimulation of PA activity by these agonists decreased with the duration of culture irrespective of the stage of follicular development. This decrease in PA activity was not associated with a change in PA inhibitor activity. Whereas two enzyme activities corresponding to 55 and 30 kDa were observed in culture of undifferentiated granulosa cells, only the high molecular weight species was detectable in the differentiated cells and was regulated by the gonadotropin and the peptides. Whereas GRF and VIP (1 μM) enhanced basal and FSH-stimulated progesterone (P) and 20α-dihydroprogesterone (20α-OH-P) secretion by undifferentiated granulosa cells, only basal progestin production were stimulated by the peptides in differentiated cells. GRF, but not VIP, stimulated granulosa cell DNA synthesis, a response independent of the stage of follicular development and markedly suppressed by FSH. The earlier demonstration of GRF and VIP secretion by ovarian cells and the presently observed influence on the proliferative and differentiative responses of granulosa cells to these peptides in vitro suggest that they play an important role in the intra-ovarian regulation of follicular development.

EFFECT OF NEUTRAL ENDOPEPTIDASE ON PLASMA AND TISSUE CONCENTRATIONS OF VASO‐ACTIVE INTESTINAL PEPTIDE

1. This study sought to determine if neutral endopeptidase metabolizes vaso-active intestinal peptide (VIP) and whether changes in the activity of this enzyme might explain the change in VIP metabolism which follows gastric sodium loading. The study also investigated whether prolonged inhibition of neutral endopeptidase was associated with inhibition of further secretion of VIP. 2. Male Sprague-Dawley rats were given the neutral endopeptidase inhibitor UK77,568 (10 mg/kg), or vehicle, tail vein injected, once or daily for 4 days. Two hours after injection the rats were anaesthetized, blood sampled to determine plasma concentrations of VIP and the hearts were harvested. Plasma and tissue concentrations of VIP were determined by radio-immunoassay. 3. Plasma VIP increased in response to UK77,568 at day 1 (P < 0.0005) but did not differ from control at day 4. The concentration of VIP in the heart did not increase at day 1 but had increased significantly at day 4 (P < 0.01). 4. It was concluded that neutral endopeptidase may metabolize VIP. Further, the increased concentration of VIP in the heart and the return of its plasma concentration to control levels at day 4 may be consistent with suppression of continued VIP secretion.

Substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide increase in nasal secretions after allergen challenge in atopic patients

Background: There is suggestive evidence that neuropeptides participate in allergic reactions. Substance P (SP) and calcitonin gene-related peptide (CGRP) are released by sensory nerves, whereas vasoactive intestinal peptide (VIP) is released mainly by parasympathetic nerves. Both sets of nerves are thought to be stimulated by allergic inflammation. The aim of this study was to assess nasal secretions to determine whether SP, CGRP, and VIP were increased after allergen challenge. Methods: Eight patients with allergic rhinitis were challenged nasally with 1 mg histamine or increasing doses of allergen. Nasal lavages were collected into a cocktail of protease inhibitors in order to restrict neuropeptide degradation. Radioimmunoassay for SP, CGRP, and VIP were performed on each sample. Results: All patients had immediate clinical reactions to both histamine and allergen challenges, and seven patients experienced a later allergic reaction. After histamine challenge, SP and CGRP did not increase significantly above baseline in the nasal lavages, whereas VIP did ( p < 0.02). In contrast, SP, CGRP, and VIP all significantly increased immediately after allergen challenge and returned to baseline within 2 hours. At the clinical peak of the late allergic reaction, SP, but not CGRP or VIP, was increased slightly but significantly ( p < 0.01). Conclusions: Thus SP, CGRP, and VIP are found in nasal secretions after allergen challenge, which confirms that neuropeptides are released in human beings during allergic reactions. The selective stimulation of VIP secretion by histamine challenge suggests that histamine-induced cholinergic reflexes induce the release of VIP. These data support the suggestion that neuropeptides may be partly responsible for some of the nasal symptoms of allergy.

Quantification of vasoactive intestinal peptide immunoreactivity in the anterior pituitary glands of intact male and female, ovariectomized, and estradiol benzoate-treated rats.

There are considerable data suggesting that vasoactive intestinal peptide (VIP) is involved in the regulation of PRL secretion; however, the role and cell of origin of anterior pituitary VIP remain to be determined. Immunocytochemical (ICC) studies have generally failed to detect VIP-immunoreactive (IR) cells in the pituitary of the untreated rat, although VIP-IR cells have been observed in the pituitaries of hypothyroid or estrogen-treated rats. This study was designed to examine the cellular distribution and tissue content of VIP in the anterior pituitary gland of rats under selected endocrine conditions known to alter the rates of PRL and VIP synthesis and secretion. To this end, anterior pituitary VIP and PRL content (ICC and RIA) and serum PRL levels were determined in ovariectomized (OVX) and OVX rats 3 days after treatment with 7 or 70 micrograms estradiol benzoate (EB). For comparison, pituitary VIP and PRL content (ICC and RIA) and serum PRL levels in untreated male and diestrous female rats were determined. Immunostaining for VIP was accomplished using a newly developed primary antiserum. Significant numbers of VIP-IR cells per 5-microns section were found in the anterior pituitary glands of all animals examined (275 +/- 33 in diestrous to 481 +/- 103 cells in male rats). VIP was not colocalized with PRL in any of the pituitaries regardless of steroid treatment or sex. Furthermore, the number of VIP-IR cells per pituitary gland was not significantly correlated with sex or EB treatment. Treatment with 70 micrograms, but not 7 micrograms, EB significantly increased the pituitary content of VIP and serum PRL levels compared to those after ovariectomy. However, both EB treatments resulted in a significant increase in pituitary PRL content compared to that in untreated OVX rats. Pituitaries from male rats had several-fold more VIP and less PRL content than pituitaries from diestrous rats. These data show that 1) in contrast to previous ICC studies, VIP-IR cells are readily detected in the anterior pituitary of intact male and female and OVX as well as EB-treated rats; 2) VIP is localized to cells other than lactotrophs, regardless of the steroid background; and 3) marked changes in anterior pituitary VIP content are not accompanied by changes in VIP-IR cell number.

The effects of a high sodium diet on the metabolism and secretion of vasoactive intestinal peptide in the rabbit.

1. In view of previous observations that the metabolism of vasoactive intestinal peptide (VIP) is significantly increased in sodium-depleted rabbits, we wished to determine whether a high sodium intake also leads to alterations in VIP metabolism. We performed metabolic clearance studies in rabbits maintained on a high sodium diet and normal control diets. These studies were performed both before and after the administration of 1.5 mmol kg-1 of sodium intravenously to observe the effects of an acute increase in body sodium. 2. The rabbits maintained on the high sodium diet had a significantly lower basal plasma VIP level (P less than 0.025), a lower metabolic clearance rate (MCR) of the peptide (P less than 0.025) and a lower secretion rate (P less than 0.005), compared with the normal control animals. These differences were maintained following the intravenous sodium infusion. 3. The administration of the intravenous sodium infusion resulted in a further decrease in MCR in the rabbits on the high sodium diet (P less than 0.05). 4. These results confirm that VIP metabolism is affected by high dietary intake of sodium, as well as a low sodium intake, adding further support to the hypothesis that VIP may be involved in sodium homeostasis.

Divergent effects of glucocorticoid on the gene expression of vasoactive intestinal peptide in the rat cerebral cortex and pituitary.

We investigated the effects of glucocorticoid on the expression of the vasoactive intestinal peptide (VIP) gene, a neuropeptide and an established prolactin (PRL)-releasing factor, in the rat brain and pituitary. The mRNA and peptide contents of VIP in the cerebral cortex, hypothalamus and anterior pituitary of male Sprague-Dawley rats were quantitated 4 weeks after adrenalectomy or sham-operation. Following adrenalectomy, VIP mRNA content increased in the anterior pituitary but showed no significant change in the cerebral cortex and hypothalamus. Dexamethasone treatment for 10 days abolished the effect of adrenalectomy and decreased significantly pituitary VIP mRNA content in sham-operated rats. In the cerebral cortex, however, dexamethasone treatment resulted in an enhancement in VIP mRNA levels in both sham-operated and adrenalectomized animals. Hypothalamic VIP mRNA content remained unchanged. These changes in VIP mRNA levels were accompanied by parallel changes in VIP concentrations in the tissues studied, suggesting that glucocorticoid regulates the synthesis of VIP in the cerebral cortex and anterior pituitary. On the other hand, serum PRL level increased after adrenalectomy but became suppressed following dexamethasone administration, in parallel with changes in pituitary VIP synthesis. These findings suggest that the effect of glucocorticoid on PRL secretion may be mediated, at least in part, via changes in VIP synthesis and secretion. We conclude that glucocorticoid regulates the expression of VIP in the rat brain, resulting in divergent changes in the cerebral cortex and pituitary. Changes in VIP synthesis and secretion may contribute to the disturbances in brain function and PRL secretion in conditions of glucocorticoid excess.

Effect of ACTH on VIP and Galanin Release from the Pituitary*

The effect of adrenocorticotropin (ACTH) on the release of four regulatory peptides from the anterior pituitary of male rats has been studied using an in vitro perfusion system. Quartered anterior pituitaries from male adult Wistar rats were perfused with buffer containing different concentrations of ACTH and, subsequently, 56 mM KCl. Fractions of 1.5 ml were collected at 3 min intervals and analyzed for vasoactive intestinal peptide (VIP), galanin, 7B2, and substance P, using specific radioimmunoassays. Concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH produced increases of 117 +/- 50%, 155 +/- 90%, 163 +/- 14%, and 161 +/- 3% (mean + SE), respectively, of basal release of VIP (P less than 0.001). However, concentrations of 1 microM and 2 microM ACTH suppressed VIP release to 74 +/- 6% and 47 +/- 4%, respectively, compared to basal release (P less than 0.001). Results for galanin release were similar: concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH increased galanin release to 129 +/- 4%, 136 +/- 8%, 143 +/- 9%, and 133 +/- 9% of basal release (P less than 0.001) and 1 and 2 microM ACTH provoked a suppression of 52 +/- 7% and 50 +/- 13%, respectively, compared with basal release (P less than 0.001). Doses of ACTH that altered the secretion of VIP and galanin had no effect on 7B2 and substance P release. These results demonstrate that ACTH causes a release of pituitary VIP and galanin in vitro and, moreover, that this is a biphasic phenomenon.

Estrogen Regulates the Gene Expression of Vasoactive Intestinal Peptide in the Anterior Pituitary

Vasoactive intestinal peptide (VIP), a prolactin (PRL)-releasing factor, has been shown to be synthesized within the anterior pituitary. To test the hypothesis that estrogens increase PRL secretion, at least in part, by stimulating VIP secretion, the concentrations of VIP, peptide histidine isoleucine (PHI) and prepro VIP mRNA were measured in the anterior pituitaries of oophorectomized rats treated with 17 beta-estradiol benzoate 25 micrograms/kg/day s.c. for 5 days. For comparison, changes in the hypothalamus were also measured. Estrogen treatment resulted in a marked increase in pituitary VIP content without detectable changes in PHI content, suggesting that estrogen may regulate differentially the enzymes involved in the posttranslational processing of the VIP prohormone. A VIP mRNA-transcript of about 1.7 kilobases was detected in all tissues studied, being most abundant in the cortex, less abundant in the hypothalamus and barely detectable in the untreated pituitary. Estrogen treatment resulted in an increase in VIP gene expression in the pituitary but not in the hypothalamus or cerebral cortex. This marked increase in prepro VIP mRNA rendered possible the demonstration in the estrogen-treated pituitary of a second VIP transcript of about 1.0 kilobase which was present in only very low quantities in the cortex and hypothalamus. We conclude that estrogen regulates the gene expression of VIP in the anterior pituitary. Changes in VIP secretion may contribute to the stimulatory effect of estrogen on PRL secretion.

Synthesis and Secretion of Vasoactive Intestinal Peptide by Rat Fetal Cerebral Cortical and Hypothalamic Cells in Culture*

To establish the neurosecretory activity of brain vasoactive intestinal peptide (VIP)ergic neurons and to characterize the molecular forms of secretion of these cells, fetal cerebrocortical and hypothalamic cells were grown in primary cultures for periods up to 4 weeks, their regulation by depolarization and calcium and sodium channel active agents was studied, and the chromatographic patterns of cell and medium VIP were determined. Mechanically dispersed cultured fetal telencephalic and diencephalic cells showed a progressive increase in immunoreactive VIP in both cells and media, reaching maximum values between 110-290 pg/mg protein.culture plate on days 15-20. Immunoreactive VIP in both cells and media corresponded almost exclusively to VIP-28 on exclusion chromatography and HPLC, and was identical to the form extracted from whole fetal brain. This indicates that both the stored and secreted forms of VIP are the mature 28-amino acid-containing peptide. To determine the influence of membrane depolarization on VIP release, the potassium concentration in the medium was increased to 30 and 56 mM, inducing a marked increase in medium VIP concentrations. The effects of K+ were dependent on Ca2+ transport, since release was blocked by the addition of verapamil, a Ca2+ channel blocker (20 microM). VIP release was stimulated by Na+ channel activation using the drug veratridine (100 microM); this effect was blocked by tetrodoxin. The influence of GH-releasing factor (GRF) on VIP release was studied by adding GRF (10(-9)-10(-7) M), alone or in the presence of anti-rGRF immunoglobulins (antirat GRF immunoglobulin G) to the incubation medium. Rat GRF stimulated VIP release and the simultaneous addition of antirat GRF immunoglobulin G blocked this effect. These findings confirm that VIP regulation by brain cells corresponds to the well defined patterns of membrane activation observed in other neuronal systems. They, furthermore, demonstrate that VIP release is under GRF influence.

Vasoactive intestinal peptide in the normal and inflamed feline gallbladder

Intravenous infusion of vasoactive intestinal peptide (VIP) causes gallbladder mucosal fluid secretion by an action on epithelial cell receptors in the cat. Gallbladder fluid secretion is observed also in experimental cholecystitis and this secretion is abolished when the intramural gallbladder nerves are blocked. In the present study, immunoreactive VIP was detected in the gallbladder contents ( 29 ± 5 (S.E.M.) pM) in the obstructed lumen of the gallbladder in cats with experimental cholecystitis and gallbladder mucosal fluid secretion, but not in the normal feline gallbladder. During luminal perfusion of the gallbladder in vivo, the calculated secretion of VIP into the gallbladder lumen in animals with experimental cholecystitis was significantly higher ( 0.31 ± 0.08 (S.E.M.), pmol/h) than in controls ( 0.11 ± 0.02 (S.E.M.), pmol/h) while plasma levels of VIP were similar. Recovery of exogenously administered VIP was similar in normal and inflamed gallbladders. The present results support the hypothesis that intramural VIP-releasing nerve fibers may be activated in cholecystitis.

Favorable prognosis of vasoactive intestinal peptide-secreting ganglioneuroblastoma

We report a 2.5-year-old girl with ganglioneuroblastoma, whose presentation was the watery diarrheal syndrome due to secretion of vasoactive intestinal peptide (VIP) by the tumor. The diarrhea subsided after resection of the tumor in two stages; the child is a long-term survivor. A review of the literature disclosed survival of 36/41 (88%) children with neural tumors that secreted VIP, including 22/26 (85%) with neuroblastoma or ganglioneuroblastoma. Thirty-five of 36 children who had resection of the tumor survived (97%), although resection was sometimes incomplete. VIP may be a marker predicting maturation of ganglioneuroblastoma and a favorable outcome. Aggressive surgery is warranted for control of the watery-diarrhea syndrome.

Pituitary Vasoactive Intestinal Peptide Regulates Prolactin Secretion in the Hypothyroid Rat

In this study, we demonstrated that the cell content and basal secretion of vasoactive intestinal peptide (VIP) in primary rat pituitary cell cultures were increased in hypothyroidism. VIP release from hypothyroid pituitary cells in vitro was stimulated by thyrotropin releasing hormone (TRH 10(-8) to 10(-6) M) and growth hormone (GH)-releasing hormone (GHRH 10(-9) to 10(-8) M) but not by corticotropin-releasing hormone or luteinizing hormone-releasing hormone in concentrations up to 10(-6) M. In the presence of anti-VIP antisera, there was a significant decrease in basal prolactin secretion from cultured hypothyroid pituitary cells (p less than 0.005) indicating that VIP exerts a tonic stimulatory effect on prolactin (PRL) secretion. The increment in PRL secretion following TRH was not affected by exposure to anti-VIP indicating that PRL release after TRH is not mediated by VIP at the pituitary level. In contrast to changes in PRL, exposure to anti-VIP had no effect on basal GH secretion, indicating that the PRL changes are hormone specific. Similarly, GHRH-induced GH release was unaffected by VIP immunoneutralization.

Immunohistochemical localization of vasoactive intestinal peptide (VIP) in the circumventricular organs of the rat.

The indirect peroxidase-antiperoxidase immunohistochemical technique was used to investigate the possible presence of vasoactive intestinal peptide (VIP) in the circumventricular organs of the rat. Considerable numbers of VIP-immunoreactive fibers were seen in the pineal gland. A moderate amount of VIP-immunoreactive fibers was present in the median eminence, the posterior lobe of the pituitary and the area postrema, but only few fibers were found in the organum vasculosum laminae terminalis. No immunoreactivity was observed in the subfornical organ or the subcommissural organ. The circumventricular organs investigated were completely free of VIP-immunoreactive perikarya. In the circumventricular organs, VIP-immunoreactive fibers were visible between the parenchymal cells and in the perivascular spaces. The presence of coarse VIP-immunoreactive terminals in apposition to the portal vessels in the external layer of the median eminence indicates that VIP may be secreted directly into the pituitary portal circulation, thus influencing the anterior pituitary cells. The presence of large VIP-immunoreactive boutons in the posterior lobe of the pituitary suggests a secretion of VIP directly into the systemic circulation. In the pineal gland, a dense innervation by VIP-immunoreactive fibers was found in the peripheral superficial part of organ, with fibers penetrating into its central portion where they mainly terminate near in vicinity of the capillaries. In the area postrema, VIP-immunoreactive material was mainly found at the ventral border of the organ. In addition to the secretion of VIP into the bloodstream via the circumventricular organs, this study provides evidence that VIP exerts specific influence on the cellular elements of these organs.

Evidence for Prolactin Feedback Actions on Hypothalamic Oxytocin, Vasoactive Intestinal Peptide and Dopamine Secretion

Ovariectomized rats, when transplanted with 4 anterior pituitaries (APs) to the kidney capsule for 2-3 weeks, had elevated plasma prolactin (PRL) levels (3.8-fold) and showed decreased in situ AP weights (0.62-fold) and PRL concentrations (0.63-fold). The concentrations of dopamine (DA) and oxytocin (OT) in pituitary portal plasma of hyperprolactinemic rats were increased 1.7- and 1.9-fold, respectively. However, the levels of vasoactive intestinal peptide (VIP) in pituitary portal plasma of these rats were decreased 0.31-fold. The secretion of DA, dihydroxyphenylalanine (DOPA) and OT from fetal hypothalamic cells in primary culture was increased, whereas VIP secretion from these cells was reduced in a dose-dependent fashion following PRL treatment. These data are the first in vivo and in vitro demonstration of a stimulatory action of PRL on OT release and an inhibitory action of PRL on VIP release. Furthermore, these data suggest that a subtle imbalance between the secretion of the PRL-inhibiting factor (DA) and the PRL-releasing factors (VIP and OT) during elevated systemic levels of PRL is responsible for decreased lactotrophic function.

Synthesis and Secretion of Vasoactive Intestinal Peptide and VIP‐Prohormone by Fetal Rat Brain Cells in Culture

Synthesis and Secretion of Vasoactive Intestinal Peptide and VIP‐Prohormone by Fetal Rat Brain Cells in Culture

Vasoactive intestinal peptide secreting tumors. Pathophysiological and clinical correlations.

Vasoactive intestinal peptide secreting tumors. Pathophysiological and clinical correlations.

Vasoactive intestinal peptide stimulates adrenal aldosterone and corticosterone secretion.

Vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers have been demonstrated in the rat adrenal cortex in close association with zona glomerulosa cells, suggesting neural regulation of adrenocortical cell function (5). The present studies were undertaken to study the possible role of VIP in the regulation of steroid hormone secretion from the outer zones of the normal rat adrenal cortex. Capsule-glomerulosa preparations, consisting of the capsule, zona glomerulosa, and a small but variable portion of the zona fasciculata, were perifused in vitro. To assess the secretory responsiveness of the capsule-glomerulosa preparation, aldosterone and corticosterone release were measured after stimulation with ACTH and angiotensin II. ACTH (10(-12)-10(-8) M) stimulated dose-dependent increases in aldosterone secretion (1.9- to 36.9-fold increases over basal values) and corticosterone secretion (1.4- to 14.0-fold increases over basal values). Angiotensin II (10(-8)-10(-5) M) stimulated dose-dependent increases in aldosterone secretion (1.6- to 8.8-fold increases over basal values). VIP (10(-6)-10(-4) M) stimulated dose-dependent increases in both aldosterone (1.7- to 41.0-fold) and corticosterone secretion (1.8- to 5.3-fold). However, glucagon and (N-Ac-Tyr1-D-Phe2)GRF-(1-29)NH2, peptides structurally related to VIP, stimulated neither aldosterone nor corticosterone secretion, indicating that VIP effects are likely to be specific for this peptide. It is noteworthy that in this preparation, the stimulation of corticosteroid secretion by VIP at 10(-5) and 10(-4) M was comparable to those by 10(-6) M angiotensin II and 10(-9) M ACTH, respectively. These results support the hypothesis that the VIP innervation of the adrenal cortex may contribute directly to the regulation of adrenal steroidogenesis.

Recurrent ganglioneuroblastoma with loss of secretion of vasoactive intestinal peptide and 4-hydroxy-3-methoxy mandelic acid

A case of ganglioneuroblastoma with severe diarrhea and increased secretion of vasoactive intestinal peptide (VIP) and 4-hydroxy-3-methoxy-mandelic acid (HMMA) is described. Ten months after surgical excision of the tumor, the patient presented with recurrent ganglioneuroblastoma without diarrhea and loss of the biochemical tumor markers. VIP and HMMA should not be used solely for the follow-up of this condition.

Cholinergic and VIPergic vasodilator actions of parasympathetic nerves on the thyroid blood flow in rats.

The present experiment was performed to investigate the effect of stimulating the parasympathetic superior laryngeal nerve (SLN) on thyroid blood flow and its mediator substances in urethane-chloralose anesthetized rats. Thyroid blood flow was measured by counting number of blood drops from a thin catheter inserted into the thyroid vein. SLNs were cut bilaterally and their peripheral portions were electrically stimulated. Electrical stimulations (intensity, 10 V; pulse duration, 0.5 ms) of SLNs increased thyroid blood flow in a frequency-dependent manner as stimulus frequencies increased from 2 to 40 Hz. The intravenous administration of atropine (0.5 mg/kg) reduced these responses, but did not abolish them. The basal secretion rate of vasoactive intestinal peptide (VIP) from thyroid glands in the resting state was nearly zero (0.25 +/- 0.14 pg/(kg.min)). SLN stimulation increased markedly the VIP secretion rate to 3.40 +/- 0.64 pg/(kg.min). The VIP secretion responses evoked by SLN stimulation remained in atropinized rats. Furthermore, exogenously applied VIP increased the thyroid blood flow dose-dependently. These results suggest that SLN stimulation increases the thyroid blood flow by dilating thyroid blood vessels via activation of cholinergic and non-cholinergic (probably VIP-containing) nerve fibers. Thus, these parasympathetic vasodilation systems may play a supplementary role in regulating the secretion of thyroid hormone by changing the thyroid blood flow in addition to the role of hormonal regulation by the thyroid stimulating hormone (TSH).