Plasma Vasoactive Intestinal Polypeptide Concentration Research Articles

Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females

Vasoactive intestinal polypeptide (VIP) is a neuroendocrine peptide distributed throughout the human body, including the CNS, where it is particularly abundant in brain regions associated with anxiety and depression. Based on earlier studies indicating that peripheral VIP may cross through the blood–brain barrier, we hypothesized plasma VIP levels to be associated with symptoms of anxiety and depression, as well as brain volume and resting-state functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex. Plasma VIP concentrations and anxiety/depression symptoms were measured in 37 healthy females. Functional and structural magnetic resonance imaging were used to evaluate functional connectivity and brain volume respectively, and their associations with VIP concentrations within brain regions associated with anxiety and depression. Negative correlations were found between VIP levels and symptoms of anxiety (r = − 0.44, p = 0.002) and depression (r = − 0.50, p = 0.001). Functional connectivity demonstrated significant VIP-dependent positive associations between the amygdala seed region with both the right parahippocampus (t(33) = 3.1, pFDR = 0.02) and right lateral orbitofrontal cortex (OFC; t(33) = 2.9, pFDR = 0.02). Moreover, VIP concentrations were significantly, positively correlated with brain volume in the left amygdala (r = 0.28, p = 0.007) and left lateral OFC (r = 0.29, p = 0.004). The present findings highlight a potential role for VIP in the neurobiology of affective symptoms.

Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients

Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65-70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP ( p = 0.642) and TNFα ( p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not ( p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.

Effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide in volunteers.

The effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide (VIP) was studied in 7 healthy subjects and 8 subjects with the common cold. Before terfenadine administration, the mean plasma substance P concentration of the subjects with the common cold was significantly higher than that of the healthy subjects. The increased mean plasma substance P concentration of the subjects with the common cold was decreased after terfenadine administration. In the healthy subjects, the mean plasma substance P concentration was unchanged by terfenadine administration. The mean plasma VIP concentration of the subjects with common cold was slightly higher than that of the healthy subjects before and after terfenadine administration, with no significant difference.

Alteration of aquaporin mRNA expression after small bowel resection in the rat residual ileum and colon.

Diarrhea occurring after small bowel resection gradually improves due to intestinal adaptation. It is known that several water channels, termed aquaporins (AQP), are expressed in the gastrointestinal tract and facilitate water transport. However, the changes of AQP after bowel resection remain unclear. In the present paper, the alterations in AQP mRNA expression were investigated after a massive small bowel resection in the rat residual ileum and colon. The 6-week-old male Sprague-Dawley rats (n = 15) underwent an 80% distal small bowel resection. The residual ileum and colon were dissected on postoperative day 1, 3, 5 or 7 (n= 3 on each day). Total RNA was purified from each mucosa, and the expressions of AQP and sodium-dependent glucose transporter (SGLT1) mRNA were analyzed by northern blot. The plasma vasoactive intestinal polypeptide (VIP) concentrations on the preoperative day and postoperative day 1 were assayed. In the residual small intestine, the expression of AQP-1 and AQP-3 mRNA increased significantly on postoperative day 1. The AQP-7 mRNA increased on postoperative day 3, but the AQP-4 mRNA did not change after the bowel resection. The SGLT1 mRNA gradually decreased after the bowel resection. In the colon, the expression of AQP-3 increased on postoperative day 1 and 7, but AQP-4 mRNA did not change after surgery. The AQP-8 mRNA levels increased slightly on postoperative day 7. Plasma VIP concentration did not change between preoperative day and postoperative day 1. These results indicate that several AQP, except for AQP-4, were up-regulated after a massive small bowel resection, and that AQP might play important roles during adaptation.

Alterations in colonic arterial and venous plasma neuropeptide concentrations in horses during low-flow ischemia and reperfusion of the large colon

Abstract Objective To measure colonic arterial (CA) and colonic venous (CV) plasma neuropeptide concentrations during low-flow ischemia and reperfusion of the large colon in horses. Animals 10 adult horses. Procedure CA and CV plasma samples collected from anesthetized horses during experimentally induced low-flow colonic ischemia and reperfusion were assayed for vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and substance P (SP), using radioimmunoassays. In 6 anesthetized horses, colonic ischemia (20% of baseline [BL]) was maintained for 3 hours, then blood flow was restored and monitored for 3 hours. Hemodynamic variables were monitored continuously and recorded at 30-minute intervals. CA resistance was calculated from colonic blood flow (Qcolon) and mean CA pressure values at each time. Blood was obtained from CA and CV catheters at 0, 1, 2, 3, 3.25, 3.5, 4, 5, and 6 hours; plasma VIP, CGRP, and SP concentrations were quantified, using radioimmunoassays. In 4 additional horses, VIP and CGRP were measured in CA and CV blood at 0, 0.25, 0.5, 0.75, and 1 hour. Results Heart rate was significantly increased at 5.5 and 6 hours; other alterations in systemic hemodynamic variables were not significant. Decrease in Qcolon during ischemia was significant; Qcolon rebounded to a value significantly greater than BL value within 5 minutes of reperfusion and was maintained above the BL value during 3 hours of reperfusion. Mean CA pressure was significantly decreased during ischemia, but returned to a value not different from the BL value by 3.25 hours. Mean CV pressure remained unchanged from the BL value during ischemia, but increased to a value significantly greater than the BL value by 3.25 hours and remained increased through 6 hours. CA resistance began to decrease during early ischemia and was significantly less than the BL value by 3.25 hours; it remained less than the BL value through 4 hours. Increase in CV VIP concentration was significant by 0.25 hour of ischemia, but decreased to a value not different from BL value by 3.25 hours. Increase in CV CGRP was significant at 3.25 hours, but this variable returned to a value not different from BL value by 3.5 hours. Conclusions CV VIP concentration increases during low-flow colonic ischemia, and CV and CA CGRP and CA SP concentrations increase during early reperfusion. (Am J Vet Res 1996;57:1200-1205)

Effect of intraduodenal bile and taurodeoxycholate on exocrine pancreatic secretion and on plasma levels of vasoactive intestinal polypeptide and somatostatin in man.

Intraduodenal (i.d.) application of bile or Na-taurodeoxycholate (TDC) dose dependently enhances basal exocrine pancreatic secretion. The hydrokinetic effect is mediated at least in part by secretin. This study should show, whether vasoactive intestinal polypeptide (VIP), a partial agonist of secretin, may also be involved in the mediation of the hydrokinetic effect. Furthermore, plasma concentrations of somatostatin-like immunoreactivity (SLI) were measured in order to check whether this counterregulating hormone is also released by bile and TDC. Twenty investigations were carried out on 10 fasting healthy volunteers provided with a double-lumen Dreiling tube. Bile and TDC were intraduodenally applied in doses of 2-6 g and 200-600 mg, respectively, at 65-min intervals. Plasma samples were withdrawn at defined intervals for radioimmunological determination of VIP and SLI. Duodenal juice was collected in 10-min fractions and analyzed for volume, pH, bicarbonate, lipase, trypsin, and amylase. I.d. application of bile or TDC dose dependently stimulated hydrokinetic and ecbolic pancreatic secretion. Bile exerted a slightly stronger effect than TDC. Pancreatic response was simultaneously accompanied by a significant increase of plasma VIP and SLI concentrations. The effect of bile on integrated plasma VIP and SLI concentrations seems to be dose dependent; the effect of TDC on integrated SLI, too. For the increase of integrated plasma VIP concentrations after TDC no dose-response relation could be established. We conclude that VIP may be a further mediator of bile-induced volume and bicarbonate secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasoactive Intestinal Polypeptide (VIP) Secretion and Refractory Diarrhea in Patients with AIDS or AIDS-Related Complex (ARC)

Elevated plasma levels of vasoactive intestinal polypeptide (VIP) (as assessed by a radio-immunoassay), were found in 7/11 patients with AIDS or AIDS-related Complex (ARC), evaluated because of prolonged intractable diarrhea with either an infectious (6 cases) or a non-infectious (5 cases) etiology. Six subjects have been treated with the somatostatin analogue octreotide, which gave both a favourable clinical response and a significant reduction in plasma VIP concentrations. Evaluation of plasma VIP levels may provide a pathophysiological basis for explaining the efficacy of octreotide therapy in HIV-infected patients suffering from both infectious and non-infectious refractory diarrhea.

Pathophysiological Characteristics of Cutaneous Microcirculation in Patients with Liver Cirrhosis: Relationships to Cardiovascular Hemodynamics and Plasma Neurohormonal Factors

To elucidate pathophysiological characteristics of the peripheral circulation in liver cirrhosis, cutaneous microcirculation was analyzed at the finger, palm, toe, and arch of the foot using laser Doppler spectroscopy in 19 patients with liver cirrhosis, and the results were correlated with cardiovascular hemodynamics ( n = 10) and plasma neurohormonal factors ( n = 8). Cutaneous blood flow at each area was all significantly reduced ( P < 0.001, < 0.05, < 0.01, < 0.001, respectively) in patients with liver cirrhosis compared to those in normals ( n = 20). Cutaneous blood mass was also significantly reduced ( P < 0.05, < 0.01, < 0.001, respectively) except at the arch of foot in patients with liver cirrhosis. There were significant correlations between finger cutaneous blood flow and systemic vascular resistance ( r = -0.73, P < 0.05), plasma norepinephrine level ( r = -0.84, P < 0.01), plasma renin activity ( r = -0.77, P < 0.01), plasma concentrations of aldosterone ( r = -0.76, P < 0.05) and angiotensin II ( r = -0.76, P < 0.05), between palm blood flow and plasma vasoactive intestinal polypeptide concentration ( r = 0.83, P < 0.05). From these results and our previous data demonstrating increased forearm muscular blood flow in patients with liver cirrhosis, increases in arteriovenous anastomotic flow and the contribution of neurohormonal factors will represent pathophysiological mechanisms for these changes.

Plasma vasoactive intestinal polypeptide concentration determination in patients with diarrhea

Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers (n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean ± SE, 28 ± 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5–9.0 mg/dL (397–795 μmol/L)] had an elevation to > 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations >76 pg/mL. In this group, 5 patients had functioning (VIP, 160–5975 pg/mL) and 5 had nonfunctioning (VIP, 80–120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known causes of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations >140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course.

VASOACTIVE INTESTINAL POLYPEPTIDE AND HUMAN VAGINAL BLOOD FLOW: COMPARISON BETWEEN TRANSVAGINAL AND INTRAVENOUS ADMINISTRATION

1. The present study was performed to examine and compare the effect of increasing doses of vasoactive intestinal polypeptide (VIP) on vaginal blood flow following vaginal subepithelial and intravenous injection in normal women. 2. Local vaginal blood flow was measured by a heated oxygen electrode. 3. Peripheral blood samples were collected throughout the experiments for VIP analysis by radioimmunoassay. 4. Both subepithelial and intravenous injections induced a significant and dose-dependent increase in vaginal blood flow (P less than 0.05), displaying the same efficacy, potency and sensitivity. 5. The vaginal flow values correlated with the corresponding plasma VIP concentrations after both routes of administration. 6. The systemic vascular side effects; that is, flushing, hypotension and tachycardia, were observed following both subepithelial and intravenous injection. 7. The findings indicate that the effect of VIP on vaginal blood flow irrespective of route of administration is part of a systemic vasodilatory effect rather than a local response.

Plasma Gastrointestinal Hormones during Spontaneous and Induced Menstrual Cycles*

Plasma levels of secretin, vasoactive intestinal polypeptide (VIP), somatostatin (SRIH), motilin, and/or pancreatic polypeptide, as well as serum estradiol, progesterone, PRL, LH, FSH, and/or GH were measured during the follicular phase, midcycle, and luteal phase of a spontaneous menstrual cycle in eight women and during ovarian stimulation with clomiphene citrate/human menopausal gonadotropin and hCG for in vitro fertilization in nine women. Plasma SRIH concentrations were significantly (P less than 0.02) higher in the luteal phase of spontaneous menstrual cycles than in follicular phase and midcycle. Serum GH levels, however, did not change. Plasma motilin concentrations also were higher in the luteal phase than at mid-cycle (P less than 0.04). Plasma secretin, VIP, and pancreatic polypeptide concentrations did not change during the cycle. Throughout the spontaneous menstrual cycle we found significant positive correlations between plasma SRIH and serum progesterone (P less than 0.007; r = 0.5869), plasma motilin and serum progesterone (P less than 0.02; r = 0.5331), plasma secretin and serum estradiol (P less than 0.04; r = 0.4711), and plasma secretin and serum PRL (P less than 0.02; r = 0.5507). During ovarian stimulation both plasma secretin and VIP gradually increased to a peak on cycle days 0 and 1, respectively (day 0 = the day of hCG injection), whereas plasma SRIH did not change. Serum estradiol and PRL increased significantly, and both peaked on cycle day 1. During ovarian stimulation plasma secretin correlated significantly with serum estradiol (P less than 0.00001; r = 0.9333), serum PRL (P less than 0.03; r = 0.6521), and plasma VIP (P less than 0.03; r = 0.6534). In addition, plasma VIP and serum PRL both correlated significantly with serum estradiol (P less than 0.05; r = 0.6024 and P less than 0.04; r = 0.6384, respectively). These results indicate 1) a possible effect of progesterone on the release of SRIH and motilin during the spontaneous menstrual cycle; 2) the unaltered serum GH concentrations in the luteal phase of the spontaneous menstrual cycle despite elevated plasma SRIH levels are probably due to a stimulatory effect of both progesterone and motilin on GH release; and 3) the increase in plasma secretin and VIP concentrations during ovarian stimulation is probably secondary to the concomitant increase in serum estradiol and/or PRL. We suggest that estradiol and/or PRL beyond a certain threshold level stimulate the release of secretin, and possibly also VIP, into plasma.

Changes in postprandial release patterns of gastrointestinal hormones in late pregnancy and the early postpartum period.

Intestinal transit time increases and gastrointestinal incretin effect is reported to decrease in pregnancy. The release patterns of gastrointestinal hormones related to these functions were studied in eight women before and after ingestion of a standardized meal at 32-34 weeks gestation and at 4 days postpartum. Basal plasma motilin and the integrated meal response of motilin, pancreatic polypeptide (PP) and gastric inhibitory polypeptide (GIP) were significantly lower in pregnancy than postpartum. The meal-induced rise of somatostatin and vasoactive intestinal polypeptide (VIP) was, however, absent in late pregnancy; whereas the somatostatin response recovered postpartum, and the plasma VIP concentrations stabilized at significantly higher levels postpartum without any meal response. Basal and meal-induced plasma insulin were significantly higher in pregnancy.

The role of vasoactive intestinal polypeptide in the inhibition of antral and pyloric electrical activity in rabbits

The nature of the neurotransmitter released by intramural non-cholinergic non-adrenergic inhibitory neurones and the type of vagal afferents involved in the inhibition of antral and pyloric electrical activity induced by vagal afferent stimulation were investigated in conscious rabbits in which both splanchnic nerves had previously been cut. The inhibitory effect of duodenal distension was reversed by bilateral thoracic vagotomy. Either intravenous or intra-aortic infusions of vasoactive intestinal polypeptide (VIP) inhibited the electrical activity of both antrum and pylorus for several minutes. Electrical stimulation of afferent vagal fibres and duodenal distension both inhibited antral and pyloric activity and produced a significant increase of portal plasma VIP concentration. Numerous VIP-immunoreactive fibres were found to be present in the muscular layers of the pylorus. The possibility that this form of inhibition is mediated by VIPergic fibres is discussed as is the likely involvement of vagal afferent fibres in the case of the response to duodenal distension.

Increase in plasma vasoactive intestinal polypeptide (VIP) in muscular exercise in humans

1. 1. We have previously shown that plasma vasoactive intestinal polypeptide (VIP) is increased in normal subjects by low-frequency transcutaneous nerve stimulation. The latter may also increase short-term physical performance in athletes (running, swimming and ergometer cycling). 2. 2. The present study examines whether the plasma VIP level is similarly increased in short-term ergometer exercise in seven healthy volunteers. 3. 3. A group of four patients with angina pectoris were included, since a lowered concentration of VIP is found in diseased heart tissue. 4. 4. In the group of healthy subjects, ergometer exercises with progressive increases in workload until exhaustion, lasting from 16 to 32 min (mean 26 min) and with a corresponding maximum energy output of 1500 to 5100 W (mean 3560 W), resulted in an increase in plasma VIP concentration from a pre-stimulatory level of 3.3 pmol·1 −1 to 5.3, 5.2 and 5.6 pmol·1 −1, measured 3, 10 and 20 min respectively, following termination of the exercise, i.e. a maximal 70% increase. 5. 5. In the patients with angina pectoris there was no significant VIP increase (cycling time 7–15 min, work performed 400–1350 W). 6. 6. Possible triggering mechanisms for VIP release and its source are discussed.

VIP and prolactin release in response to meals.

To determine the role of vasoactive intestinal polypeptide (VIP) and prolactin (PRL) in digestion, plasma VIP and PRL levels were measured in healthy, non-obese and obese premenopausal women fed isocaloric breakfasts containing a high carbohydrate or a high fat-protein content. A significant increase in plasma VIP concentration occurred after a high fat-protein breakfast, the increase being independent of body mass index. Plasma PRL level was unaltered by breakfast. Results suggest that the release of VIP after a meal depends on a high fat concentration in the duodenum, which may then stimulate bicarbonate release and fat-stimulated release of cholecystokinin.

Gastric and intestinal release of vasoactive intestinal polypeptide in the milk-fed lamb

Vasoactive intestinal polypeptide (VIP) has been proposed as the neurotransmitter of the atropine-resistant relaxation of gastric structures in the lamb. To examine this proposal VIP concentrations in plasma from arterial, gastric venous and intestinal venous blood were measured in healthy conscious lambs before, during and after teasing with, and sucking of milk. Basal arterial plasma VIP concentrations were undetectable (<3 pmol/l) and remained so during and after feeding. Before feeding VIP was detected in only 2 of 12 gastric venous plasma samples (5 and 13 pmol/l). During teasing with food there were increments in VIP of 19 ± 4 pmol/l and during feeding of 27 ± 5 pmol/l . VIP concentration in gastric venous plasma rapidly returned to fasting levels after cessation of sucking. In contrast VIP in the intestinal venous plasma did not rise during teasing or upon commencement of sucking but a peak increment of 34 ± 6 pmol/l occurred at 5 min after cessation of feeding. The results are consistent with the hypotheses that VIP is released in anticipation of and during sucking from inhibitory neurones involved in relaxation of gastric structures and that intestinal release of VIP is a consequence of entry of digesta into the small intestine.

Production of Secretory Diarrhea by Intravenous Infusion of Vasoactive Intestinal Polypeptide

We attempted to reproduce the diarrhea of pancreatic cholera syndrome with prolonged (10-hour) administration of vasoactive intestinal polypeptide (VIP) in five healthy nonfasting subjects. The polypeptide was given as a continuous intravenous infusion at a rate of 400 pmol per kilogram of body weight per hour. By two hours the plasma VIP concentration had risen from a normal basal value of 15.3 +/- 0.2 (mean +/- S.E.M.) to 129 +/- 40 pmol per liter--within the range found in patients with pancreatic cholera syndrome. In each subject profuse watery diarrhea developed within 4.3 +/- 0.8 hours (range, 2.0 to 6.3), and the mean stool weight at 10 hours was 2441 +/- 600 g (normal 24-hour stool weight, less than 200 to 250 g). The results of stool analysis were consistent with secretory diarrhea. Between the first and last stool, there were significant increases in fecal sodium and bicarbonate concentrations and in pH. The large fecal bicarbonate loss induced hyperchloremic metabolic acidosis, which is characteristic in patients with pancreatic cholera syndrome. Our study suggests that VIP is not merely a marker of pancreatic cholera, but is the mediator of watery diarrhea in this syndrome.

The effect of vasoactive intestinal polypeptide on meal-stimulated gastric acid secretion in man.

The effect of vasoactive intestinal polypeptide (VIP) on meal-stimulated gastric acid secretion was studied in six healthy volunteers. Acid secretion was stimulated by instillation of a 10% solution of peptone, which was adjusted to pH 5.5, circulated through the stomach via a double-lumen gastric tube by a peristaltic pump. The acid secretion was estimated by continuous titration by a pH-stat. The subjects were studied twice on separate days, receiving an intravenous infusion of either VIP (1 microgram/kg/h) or saline. No effect on acid secretion was found. Mean serum gastrin concentration rose from 42 pmol/l to 150 pmol/l during meal stimulation and was unaffected by infusion of VIP. Plasma VIP concentration during infusion of saline was 6.8 pmol/l and during VIP infusion, 82.8 pmol/l. Plasma VIP concentration was unaffected by the peptone meal.

VASOACTIVE INTESTINAL POLYPEPTIDE (VIP) IN CHILDREN WITH NEURAL CREST TUMOURS

The concentration of vasoactive intestinal polypeptide (VIP) in plasma was measured in 22 children with neural crest tumours (NCT) during a 5-year period; the mean concentration of VIP in plasma was 22.5 pmol/l (interval 2.0-95.0 pmol/l). To establish a reference interval the plasma concentration of VIP was measured in 41 children without tumours; the mean concentration of VIP in plasma was 6.2 pmol/l (interval 0.5-19.0 pmol/l). Of the 22 children with NCT 16 had a plasma concentration of VIP within the normal range while 6 children (27%) had elevated plasma concentration of VIP between 28 and 95 pmol/l. Only one child, whose plasma concentration of VIP was 95 pmol/l had diarrhoea. Elevated plasma concentration of VIP in children with NCT but no diarrhoea has not previously been described. The urinary excretion of vanillylmandelic acid (VMA) was increased in 18 of the children with NCT (82%). In 2 of the children with normal excretion of VMA the concentration of VIP in plasma was elevated. Thus, the plasma concentration of VIP may be a supplement to VMA as a tumour marker in some cases of NCT.

Stimulation by serotonin of vasoactive intestinal polypeptide release into rat hypophysial portal blood.

The effect of serotonin (5-HT) on plasma vasoactive intestinal polypeptide (VIP) levels in hypophysial portal blood was studied in urethane-anesthetized rats. Portal blood was collected by the parapharyngeal approach and plasma VIP was determined by radioimmunoassay. Mean (+/- SE) basal plasma VIP level was 1799 +/- 232 pg/ml, which was slightly decreased during the control experiments in which physiological saline was injected either intraventricularly or intravenously. Intraventricular injection of 5-HT (2 and 10 micrograms/rat) resulted in a significant increase in plasma VIP concentrations within 20 min. Intravenous injection of L-5-hydroxytryptophan (5-HTP, 1 mg/100 g BW), a precursor of 5-HT, also caused an increase in VIP concentrations in hypophysial portal plasma. The flow rate of hypophysial portal blood did not change throughout the experiments. These findings suggest that 5-HT stimulates VIP release from the median eminence into the hypophysial portal vessels in the rat.