Protecting effects of vasoactive intestinal polypeptide on lymphocytes against metal toxicity.

The hormonal neuropeptides calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), were investigated for a potential protective effect on thymocytes after a toxic dose of nickel sulfate, giving an inhibition of DNA synthesis. There was a statistically significant increase in the synthesis of DNA from the level caused by nickel sulfate, with VIP, 10(-4)-10(-5) mol/l, while the slightly stimulating effects obtained with CGRP, CCK and NPY, were statistically non-significant. This indicates that VIP, at least as pharmacological concentrations, might have protective effects on lymphocytes against metal toxicity.     

Protecting Effects of Vasoactive Intestinal Polypeptide on Lymphocytes Against Metal Toxicity

The hormonal neuropeptides calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), were investigated for a potential protective effect on thymocytes after a toxic dose of nickel sulfate, giving an inhibition of DNA synthesis. There was a statistically significant increase in the synthesis of DNA from the level caused by nickel sulfate, with VIP, l0^-4-10^-5 mol/l, while the slightly stimulating effects obtained with CGRP, CCK and NPY, were statistically non-significant. This indicates that VIP, at least as pharmacological concentrations, might have protective effects on lymphocytes against metal toxicity.     

Blockade of nitric oxide decreases the renal vasodilatory effect of neuropeptide Y in the insulin-treated diabetic rat

 The effect of 50 days of streptozotocine-induced diabetes mellitus (blood glucose 20 mmol/l) on contraction and relaxation of isolated renal and intrarenal arteries in rats were examined. Strong and similar contractions were induced by potassium (60 mM), 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) in renal and intrarenal arteries in diabetic and control rats. The vasodilatory reactivity, after precontraction with 5-HT, of neuropeptide Y (NPY) was similar to that of acetylcholine (ACh), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and was similar in diabetic and control rats. The relaxing effect of NPY was decreased (40%) only in the diabetic group by blockade of nitric oxide synthase with N ^G-nitro-L-arginine methyl ester (10^–4 M) and by blockade (50%) of NPY with α-trinositol (10^–6 M). In conclusion, the present study showed that diabetes mellitus in the rat is associated with normal vasoconstrictive and vasodilatory capacities. However, the vasodilatory response to NPY was largely eliminated by blockade of nitric oxide synthesis only in the diabetic animals. This indicates that the vasodilatory effect of NPY in diabetes mellitus may be dependent on nitric oxide synthesis. Received: 12 November 1996 / Received after revision: 10 March 1997 / Accepted: 7 April 1997     

Co-existence of neuropeptides and differential inhibition of vasodilator responses by neuropeptide Y in guinea pig uterine arteries

The co-localization of substance P (SP) with calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) with neuropeptide Y (NPY) of the guinea pig uterine artery were investigated with immunocytochemistry. The SP/CGRP fibre population was distinct from the VIP/NPY fibre population. Both types of fibres ran in the medial-adventitial border, and appeared as coarsed and fine varicosed. Uterine arterial dilatation was evoked by acetylcholine (ACh), SP, CGRP, and VIP in precontracted arteries as examined by a sensitive in vitro method. Strong relaxations were seen by ACh, CGRP and VIP. NPY had no relaxant effect per se but was found to be a potent inhibitor of vasodilation induced by ACh and SP, while relaxations induced by VIP and CGRP were unaffected. The functional significance of NPY in the uterine artery may to a large extent be to increase tension not only by potentiation of contraction but additionally by inhibiting vasodilator responses.     

跳伞应激对空降兵新兵神经内分泌的影响

近年来神经内分泌研究成为预防医学和军事医学的优先发展领域和研究前沿。其研究对提高空降兵部队的心理健康水平和紧急状态下的应对能力 ,最大限度减低非战斗减员的发生率具有重要意义。国外跳伞人员 (非伞兵 )神经内分泌学研究偏重于与应激有关的下丘脑—垂体—肾上腺轴系统 (皮质醇、ＡＣＴＨ等 )及内源性阿片肽的研究[1-6] ,对其它系统及神经肽的变化研究甚少。本研究就空降兵新兵群体在跳伞应激状态下精氨酸血管加压素 (ＡＶＰ)、神经肽Ｙ(ＮＰＹ)、降钙素基因相关肽 (ＣＧＲＰ)、神经降压素 (ＮＴ)、血管活性肠肽 (ＶＩＰ)的变化规律…     

Toxic rhinitis-induced changes of human nasal mucosa innervation

Irritative toxic rhinitis is a nasal disorder induced by chemical compounds like ozone, formaldehyde, nickel, chrome, solvents and tobacco smoke. These noxious stimuli may have effects on the nasal innervation leading to a cascade of neuro-immune interactions and an augmentation of the symptoms. Here we examined changes in the neuropeptide content of mucosal parasympathetic, sympathetic and sensory nerves of patients with toxic rhinitis caused by chronic cigarette smoke exposure. Semiquantitative immunohistochemistry using antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and vasoactive intestinal peptide (VIP) was carried out on cryostat sections of human nasal mucosa obtained from normal subjects and patients with toxic rhinitis and revealed significant differences between both groups. Toxic rhinitis patients had significantly elevated expression scores for VIP (2.83 +/- 0.31 vs 1.27 +/- 0.47 control group) and NPY (3.17 +/- 0.31 vs 0.91 +/- 0.37 control group) revealing an increase of mediators in distinct subpopulations of airway nerves. In summary, the present studies indicate a differential participation of subclasses of mucosal nerves in the pathophysiology of toxic rhinitis. Airway innervation may have a major role in the pathophysiology of toxic rhinitis associated with chronic cigarette smoke exposure.     

Origin and peptide content of nerve fibers in the nasal mucosa of rats

Injection of the retrograde neuronal tracer True blue into the anterior-lateral part of the nasal mucosa of rats labeled nerve cell bodies in the superior cervical ganglion, the sphenopalatine ganglion, the otic ganglion and the trigeminal ganglion on the ipsilateral side. In the superior cervical ganglion, the sphenopalatine ganglion and the trigeminal ganglion on the contralateral side, very few nerve cell bodies were labeled, indicating that these ganglia provide minor contributions only. The number of labeled cell bodies indicates that the superior cervical ganglion, the sphenopalatine ganglion and the trigeminal ganglion contribute most to the innervation of the nose, while the contribution from the otic ganglion is minor. Cell bodies in the superior cervical ganglion harbored noradrenaline (NA) or NA/neuropeptide Y (NPY); in the sphenopalatine ganglion vasoactive intestinal peptide (VIP) or VIP/NPY; in the otic ganglion VIP, VIP/NPY or VIP/substance P (SP) and in the trigeminal ganglion calcitonin gene-related peptide (CGRP) or CGRP/SP. The results from denervations and tracer experiments suggest that all NA-containing and the majority of NPY-containing fibers in the nasal mucosa are derived from the superior cervical ganglion (sympathetic nerve supply). VIP- and VIP/NPY-containing fibers originate from the sphenopalatine and otic ganglia (parasympathetic nerve supply). Nerve fibers containing CGRP and CGRP/SP emanate from the trigeminal ganglion (sensory nerve supply).     

Gene expression for peptides in neurons of the petrosal and nodose ganglia in rat

Summary In situ hybridization was used to determine whether genes for neuropeptides [substance P/neurokinin A (SP/NKA), calcitonin gene-related peptide (CGRP), somatostatin (SOM), neuropeptide tyrosine (NPY) and cholecystokinin (CCK)] are expressed in inferior ganglia of the vagus (nodose) and glossopharyngeal (petrosal) nerves. Synthetic oligodeoxyribonucleotides, complementary to the cognate, mRNAs were labeled with [³²P] or [³⁵S], and hybridized to 10 m thick sections of unperfused tissue which were then processed for film and emulsion autoradiography. We found numerous, clustered neuronal perikarya throughout the nodose and petrosal ganglia that expressed preprotachykinin A (SP/NKA) and CGRP mRNAs to varying degrees. Neurons expressing preproSOM mRNA were less abundant and more scattered throughout both ganglia. Notably, we found mRNA for NPY in cells (usually 5–10 per section) in both ganglia. To our knowledge, this is first evidence for NPY in these sensory ganglia. In contrast to previous immunohistochemical findings, we found no evidence for expression of preproCCK in either the nodose or petrosal ganglia. The present findings demonstrate that cells of the nodose and petrosal ganglia express the genes for a number of neuropeptides that are presumably involved with transmission of visceral sensory afferent information to higher order neurons of the central nervous system.     

NT-3 modulates NPY expression in primary sensory neurons following peripheral nerve injury

Peripheral nerve transection induces significant changes in neuropeptide expression and content in injured primary sensory neurons, possibly due to loss of target derived neurotrophic support. This study shows that neurotrophin-3 (NT-3) delivery to the injured nerve influences neuropeptide Y (NPY) expression within dorsal root ganglia (DRG) neurons. NT-3 was delivered by grafting impregnated fibronectin (500 ng/ml; NT group) in the axotomised sciatic nerve. Animals grafted with plain fibronectin mats (FN) or nerve grafts (NG) were used as controls. L4 and L5 DRG from operated and contralateral sides were harvested between 5 and 240 d. Using immunohistochemistry and computerised image analysis the percentage, diameter and optical density of neurons expressing calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and NPY were quantified. Sciatic nerve axotomy resulted in significant reduction in expression of CGRP and SP, and significant upregulation of VIP and NPY ( P <0.05 for ipsilateral vs contralateral DRG). By d 30, exogenous NT-3 and nerve graft attenuated the upregulation of NPY ( P <0.05 for NT and NG vs FN). However, NT-3 administration did not influence the expression of CGRP, SP or VIP. The mean cell diameter of NPY immunoreactive neurons was significantly smaller in the NT-3 group ( P <0.05 for NT vs FN and NG) suggesting a differential influence of NT-3 on larger neurons. The optical densities of NPY immunoreactive neurons of equal size were the same in each group at any time point, indicating that the neurons responding to NT-3 downregulate NPY expression to levels not detectable by immunohistochemistry. These results demonstrate that targeted administration of NT-3 regulates the phenotype of a NPY-immunoreactive neuronal subpopulation in the dorsal root ganglia, a further evidence of the trophic role of neurotrophins on primary sensory neurons.     

Peptide-containing nerves in the human pregnant uterine cervix: an immunohistochemical study exploring the effect of RU 486 (mifepristone).

The presence of several neuropeptides (neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), enkephalin (ENK), somatostatin (SOM) was established in the early pregnant human cervix using indirect immunofluorescence immunohistochemistry. Several peptides (VIP, NPY, CGRP, GAL) were present both in free nerves among smooth muscle cells and around blood vessels. Others (SP, SOM) were only seen as single varicosities among smooth muscle cells. Randomized treatment of patients with RU 486 (mifepristone) prior to surgical sampling revealed no clearcut differences in peptide immunoreactivities. After RU 486 treatment, however, there was a tendency towards a decrease of NPY- and VIP-immunoreactivity, and an increase of CGRP-immunoreactivity.     

Distribution of neuropeptides in rat pterygopalatine ganglion: light and electron microscopic immunohistochemical studies.

The distribution and quantity of neuropeptides in the rat pterygopalatine ganglion were studied by using complete serial paraffin sections of the ganglion immunostained with antiserum against several neuropeptides. The pterygopalatine ganglion, composed of 4932 +/- 291 (mean +/- SD) neurons, was triangular in shape with a tapering caudal tail. The most commonly found peptide in neurons was vasoactive intestinal polypeptide (VIP) (99.0%), followed by neuropeptide Y (NPY) (54.1%) and enkephalin (10.5%). The rostro-ventromedial and caudal parts of the ganglion where intensely VIP-immunoreactive neurons predominate project to the nasal mucosa, while the rostro-dorsolateral part of the ganglion where NPY-immunoreactive neurons predominate projects to the Harderian gland. The coexistence of VIP/NPY (47.4%), VIP/NPY/enkephalin (6.6%) or VIP/enkephalin (3.9%) in the ganglionic neurons was recognized. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive varicosities formed synaptic contacts with the somatic spine or soma, which confirmed that the reflex arch, composed of axon collaterals of trigeminal ganglionic neurons and parasympathetic ganglionic neurons, operates through direct synapses. Enkephalin-immunoreactive varicosities, which were probably derived from parasympathetic preganglionic neurons, also made synaptic contact with the somatic spine.     

Presynaptic and interactive peptidergic modulation of reticulospinal synaptic inputs in the lamprey

The modulatory effects of neuropeptides on descending inputs to the spinal cord have been examined by making paired recordings from reticulospinal axons and spinal neurons in the lamprey. Four peptides were examined; peptide YY (PYY) and cholecystokinin (CCK), which are contained in brain stem reticulospinal neurons, and calcitonin-gene-related peptide (CGRP) and neuropeptide Y (NPY), which are contained in primary afferents and sensory interneurons, respectively. Each of the peptides reduced the amplitude of monosynaptic reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The modulation appeared to be presynaptic, because postsynaptic input resistance and membrane potential, the amplitude of the electrical component of the EPSP, postsynaptic responses to glutamate, and spontaneous miniature EPSP amplitudes were unaffected. In addition, none of the peptides affected the pattern of N-methyl-D-aspartate (NMDA)-evoked locomotor activity in the isolated spinal cord. Potential interactions between the peptides were also examined. The "brain stem peptides" CCK and PYY had additive inhibitory effects on reticulospinal inputs, as did the "sensory peptides" CGRP and NPY. Brain stem peptides also had additive inhibitory effects when applied with sensory peptides. However, sensory peptides increased or failed to affect the amplitude of reticulospinal inputs in the presence of the brain stem peptides. These interactive effects also appear to be mediated presynaptically. The functional consequence of the peptidergic modulation was investigated by examining spinal ventral root responses elicited by brain stem stimulation. CCK and CGRP both reduced ventral root responses, although in interaction both increased the response. These results thus suggest that neuropeptides presynaptically influence the descending activation of spinal locomotor networks, and that they can have additive or novel interactive effects depending on the peptides examined and the order of their application.     

Neurochemical properties of the middle cervical ganglion in the sheep

The neurochemical properties of the ovine middle cervical ganglion (MCG) were studied using antibodies raised against tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and galanin (GAL). Double-labelling immunocytochemistry revealed that the vast majority (95.5 +/- 0.8%) of postganglionic sympathetic MCG neurons expressed simultaneously both catecholamine-synthesizing enzymes (neurons were TH/DbetaH-positive). A large population of noradrenergic neurons exhibited immunoreactivity (IR) to NPY (62.2 +/- 2.2%), but single NPY-positive perikarya-lacking noradrenergic markers were also observed (2.0 +/- 0.3%). None of the examined MCG neuronal somata contained SP, CGRP, GAL or VIP. A moderate number of noradrenergic nerve fibres located amongst neuronal cell bodies was also found. In small number of these terminals the presence of NPYor GAL (but not CGRP or VIP) was detected. The ovine MCG was numerously innervated with SP-immunoreactive nerve fibres which sometimes formed basket-like formations around postganglionic neurons. The MCG exhibited a sparse CGRP-immunoreactive innervation and lacked VIP-positive nerve terminals. In many aspects the chemical coding of MCG postganglionic neurons and nerve terminals resembles that found in other mammalian cervico-thoracic paravertebral ganglia, but some important species-dependent differences exist. The functional implications of these differences remain to be elucidated.     

A double-label immunohistochemical study of intramural ganglia from the human male urinary bladder neck

Double-label immunocytochemistry was used to investigate the colocalisation of various neuropeptides and the enzymes nitric oxide synthase (NOS) and tyrosine hydroxylase (TH) in intramural ganglia of the human male urinary bladder neck and trigone. Postmortem specimens were obtained from 7 male infants and children ranging in age from 2 mo to 3 y who had died as a result of cot death or accidental trauma. On average 60% of the intramural neurons were non-TH-immunoreactive (-IR) (i.e. presumptive cholinergic) and 40% were TH- and DbβH-IR (i.e. noradrenergic). Within the non-TH-IR population, calcitonin gene-related peptide (CGRP) was found in 65% of cells, neuropeptide Y (NPY) in 90%, nitric oxide synthase (NOS) in 45%, somatostatin (SOM) in 90%, and vasoactive intestinal polypeptide (VIP) in 40%. The corresponding values for the TH-IR neurons were CGRP (54%), NPY (70%), NOS (58%), SOM (73%) and VIP (40%). All the observed bombesin (BOM)-immunoreactivity was colocalised with TH while 90% of VIP and almost all the CGRP was colocalised with NPY. Less than 5% of neurons were immunoreactive for substance P (SP) or met-enkephalin (m-ENK) and some of these also contained TH. Varicose nerve fibres were seen in close proximity to some of the intramural neurons, the majority of such varicosities showing immunoreactivity to CGRP, VIP or TH. Less common were pericellular varicosities immunoreactive to NPY, SOM or SP. These results demonstrate the neurochemical heterogeneity of intramural neurons in the human bladder neck and provide indirect evidence for the complexity of the peripheral innervation of the human urinary bladder.     

Distribution and origin of nerve fibers in the rat temporomandibular joint capsule

 The distribution and origin of nerve fibers containing neuropeptides and NOS projecting to the temporomandibular joint capsule (TMJ) of the rat were studied by retrograde tracing in combination with immunocytochemistry. Numerous nerve fibers were seen in the TMJ as revealed by the neuronal marker protein gene product 9.5. Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), calcitonin gene-related peptide (CGRP), and nitric oxide synthase (NOS) were seen in the synovial membrane, the joint capsule and entering the articular disc. Injection of the retrograde tracer True Blue (TB) into the TMJ resulted in the appearance of numerous labeled nerve cell bodies in the trigeminal and superior cervical ganglia, and moderate numbers in the nodose, the otic, the sphenopalatine, the stellate and the dorsal root ganglia at levels C2–C5. Most of the TB-labeled cell bodies in the superior cervical and stellate ganglia contained NPY. In the trigeminal ganglion, numerous TB labeled cell bodies contained CGRP and a minor population stored SP, a few cell bodies were seen to store NOS or PACAP. In the sphenopalatine and otic ganglia, TB labeled cell bodies contained NOS or VIP. In the nodose ganglion, labeled cell bodies contained CGRP; other labeled cell bodies harbored NOS. In the cervical dorsal root ganglia, the majority of the labeled cell bodies stored CGRP and smaller populations stored SP and PACAP. Thus, the innervation of the TMJ is complex and many different ganglia are involved. Accepted: 13 October 1997     

Nitric oxide synthase, choline acetyltransferase, catecholamine enzymes and neuropeptides and their colocalization in the anterior pelvic ganglion, the inferior mesenteric ganglion and the hypogastric nerve of the male guinea pig

By the indirect immunofluorescence method, the distribution of nitric oxide synthase (NOS)-like immunoreactivity (LI) and its possible colocalization with neuropeptide immunoreactivities, with two enzymes for the catecholamine synthesis pathway, tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH), as well as the enzyme for the acetylcholine synthesis pathway, choline acetyltransferase (ChAT) were studied in the anterior pelvic ganglion (APG), the inferior mesenteric ganglion (IMG) and the hypogastric nerve in the male guinea pig. The analyses were performed on tissues from intact animals, as well as after compression/ligation or cut of the hypogastric nerve. In some cases the colonic nerves were also cut. Analysis of the APG showed two main neuronal cell populations, one group containing NOS localized in the caudal part of the APG and one TH-positive group lacking NOS in its cranial part. The majority of the NOS-positive neurons contained ChAT-LI. Some NOS-positive cells did not contain detectable ChAT, but all ChAT-positive cells contained NOS. NOS neurons often contained peptides, including vasoactive intestinal peptide (VIP), neuropeptide tyrosine (NPY), somatostatin (SOM) and/or calcitonin gene-related peptide (CGRP). Some NOS cells expressed DBH, but never TH. The second cell group, characterized by absence of NOS, contained TH, mostly DBH and NPY and occasionally SOM and CGRP. Some TH-positive neurons lacked DBH. In the IMG, the NOS-LI was principally in nerve fibers, which were of two types, one consisting of strongly immunoreactive, coarse, varicose fibers with a patchy distribution, the other one forming fine, varicose, weakly immunoreactive fibers with a more general distribution. In the coarse networks, NOS-LI coexisted with VIP- and DYN-LI and the fibers surrounded mainly the SOM-containing noradrenergic principal ganglion cells. A network of ChAT-positive, often NOS-containing nerve fibers, surrounded the principal neurons. Occasional neuronal cell bodies in the IMG contained both NOS- and ChAT-LI. Accumulation of NOS was observed, both caudal and cranial, to a crush of the hypogastric nerve. VIP accumulated mainly on the caudal side and often coexisted with NOS. NPY accumulated on both sides of the crush, but mainly on the cranial side, and ENK was exclusively on the cranial side. Neither peptide coexisted with NOS. Both substance P (SP) and CGRP showed the strongest accumulation on the cranial side, possibly partly colocalized with NOS. It is concluded that the APG in the male guinea-pig consists of two major complementary neuron populations, the cholinergic neurons always containing NOS and the noradrenergic neurons containing TH and DBH. Some NOS neurons lacked ChAT and could represent truly non-adrenergic, non-cholinergic neurons. In addition, there may be a small dopaminergic neuron population, that is containing TH but lacking DBH. The cholinergic NOS neurons contain varying combinations of peptides. The noradrenergic population often contained NPY and occasionally SOM and CGRP. It is suggested that NO may interact with a number of other messenger molecules to play a role both within the APG and IMG and also in the projection areas of the APG.     

Effect of substance P on CCK- or VIP-induced choleresis in anesthetized dogs

10 anesthetized dogs were provided with acute common bile duct fistulas and the gallbladder was excluded. Hepatic bile output and biliary content of sodium, potassium and amylase were studied. 6 caval infusions were administered of CCK, 0.3 Ivy U-kg^-1 min^-1, with a superimposed infusion of SP, 20 ng kg^-1 min^-1. 7 caval infusions were given of VIP, 50 ng-kg^-1 min^-1, with a superimposed infusion of SP, 20 ng·kg^-1 min^-1. CCK increased bile output and biliary content of sodium, potassium and amylase by 78–110%. The corresponding increase induced by VIP was 55–85%. Biliary pH was not influenced. SP abolished the effects of both CCK and VIP. It is suggested that all peptides studied influenced canalicular bile secretion by changing the electrolyte excretion.     

Calcitonin gene-related peptide (CGRP) receptors are linked to cyclic adenosine monophosphate production in SK-N-MC human neuroblastoma cells

Calcitonin gene-related peptide (CGRP) stimulated cyclic adenosine monophosphate (cAMP) levels in SK-N-MC human neuroblastoma cells in a time- and concentration-dependent manner. The efficacy order for CGRPs was human alpha-CGRP = human beta-CGRP = chick CGRP greater than rat CGRP greater than human [Tyr0]CGRP. Calcitonin (CT) failed to influence cAMP production in SK-N-MC cells. [Tyr0]CGRP27-37 which by itself did not affect cAMP levels antagonized CGRP action. Saturation analysis using [125I]CGRP showed a homogeneous population of binding sites. CGRP but not CT, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) inhibited radioligand binding. Our results provide evidence that human neuroblastoma SK-N-MC cells contain highly specific CGRP receptors which are positively coupled to cAMP generation.     

CGRP-induced activation of KATP channels in follicular Xenopus oocytes

The two-microelectrode voltage-clamp technique was used to monitor K⁺ channel activity in Xenopus oocyte follicular cells, which are electrically coupled to the oocyte itself by gap junctions. Endogenous vasodilators such as calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), prostaglandin E₂ (PGE₂) and adenosine activate glibenclamide-ATP-sensitive K⁺ (K_ATP) channels in Xenopus oocyte follicular cells. The mechanism of action of CGRP was studied in detail. CGRP effects undergo a rapid desensitization. CGRP acts via CGRP_I receptors. Its effects are antagonized by the amino-truncated CGRP analog hCGRP(8–37). The second messenger for CGRP activation of K_ATP channels is cAMP. Phosphodiesterase inhibition by 3-isobutyl-1-methylxanthine enhances the CGRP response while adenyl cyclase inhibition by either 2,5-dideoxyadenosine or progesterone nearly completely depresses the CGRP response. Vasoconstrictors such as ACh and angiotensin II also have receptors in follicular cells. ACh strongly inhibits the CGRP activation of K⁺ channels as it inhibits the activation of K_ATP channels by P1060, but angiotensin II does not. It is concluded that as in vascular smooth muscle cells, CGRP and probably other hyperpolarizing vasodilators open K_ATP channels in follicular cells by protein kinase A activation.Thanks are due to C. Roulinat and F. Aguila for expert technical assistance. This work was supported by the Centre National de la Recherche Scientifique (CNRS).