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Biomedical subjects

J Behar

Publications and source records attributed to J Behar.

At least 55 records · Page 3Linked to original sources
PubMed1993

Pathogenesis of simultaneous esophageal contractions in patients with motility disorders.

BACKGROUND: Simultaneous and spontaneous contractions are frequently recorded in patients with esophageal motility disorders. The aim was to investigate the pathogenesis of swallow-induced simultaneous and spontaneous contractions. METHODS: The pathogenesis was studied in patients with normal peristaltic contractions (control group) and in patients with functional dysphagia with either simultaneous contractions (group A), with peristaltic but prolonged contractions (group B), and with frequent spontaneous contractions (group C). RESULTS: Simultaneous contractions had latencies of 2.9 +/- 0.2 seconds compared with 6.4 +/- 0.2 seconds for normal peristaltic contractions and 5.8 +/- 0.4 seconds for prolonged peristaltic contractions. Paired swallows at intervals of 5 seconds generated one peristaltic sequence after the second swallow in subjects with normal peristalsis and two sets of contractions in patients with simultaneous contractions. Ten consecutive swallows taken at 5-second intervals inhibited the spontaneous contractions evoked by bethanechol in control subjects but had no significant effect on the spontaneous contractions of subjects with simultaneous contractions. Atropine reduced the frequency, force, and duration of the spontaneously generated contractions in group C. CONCLUSIONS: The shorter latency of simultaneous contractions may be caused by a defective deglutitive inhibitory reflex, and spontaneous contractions appear to be generated by swallow independent discharges of acetylcholine.

Atropine↗
PubMed1993

Inositol trisphosphate restores impaired human gallbladder motility associated with cholesterol stones.

BACKGROUND: Gallbladder motility is impaired in specimens with cholesterol stones but normal with pigment stones. METHODS: Muscle cells obtained from 19 human gallbladders with cholesterol stones and 11 with pigment stones were enzymatically digested and contracted with cholecystokinin octapeptide (CCK-8), acetylcholine, and KCl. RESULTS: Muscle cells from pigment stones had a greater contraction than cells from cholesterol stones. CCK-8-induced contraction was unaffected by calcium-free media but was blocked by strontium. Potassium-evoked contraction was blocked by a calcium-free media and unaffected by strontium. Inositol triphosphate (IP-3)-induced contraction was similar to the contraction caused by CCK-8 in permeable cells from pigment stones but was greater than the response to CCK-8 in cells from cholesterol stones. CONCLUSIONS: Muscle cells from gallbladders with cholesterol stones contract less than cells from gallbladders with pigment stones; CCK-8-induced contraction only uses stored calcium; and IP-3 causes contractions of equal magnitude in cells from gallbladders with cholesterol and pigment stones. These abnormalities could result from an impaired receptor activation of the mechanism for IP-3 generation and release of stored calcium.

Acetylcholine↗
PubMed1993

Interaction between signal transduction pathways contributing to gallbladder tonic contraction.

Muscle strips were used to study the mechanisms that generate cat gallbladder tone. Strontium substitution for calcium and the protein kinase C (PKC) inhibitor H-7 abolished the tone, whereas the calmodulin antagonist W-7 had no effect, suggesting that tone depends on intracellular calcium release and the PKC pathway. Basal levels of diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3) were higher in gallbladder muscle than in esophageal muscle, which does not maintain tone. These data suggest that IP3 might interact with DAG to activate PKC during tonic contraction. This interaction was demonstrated in single cells in which a low dose of IP3 potentiated DAG and the potentiation was blocked by H-7. Furthermore, low doses of IP3 induced contraction, which was blocked by H-7 and unaffected by the calmodulin antagonist CGS-9343B; high doses of IP3 were unaffected by H-7 but were blocked by CGS-9343B; DAG-induced contraction was blocked by activated calmodulin. We conclude that 1) the synergistic action of DAG and IP3-calcium release, which further activates PKC, might be responsible for gallbladder tone and 2) activated calmodulin appears to inhibit the effect of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Distinct muscarinic receptors, G proteins and phospholipases in esophageal and lower esophageal sphincter circular muscle.

Acetylcholine (ACh)-induced contraction of esophageal circular smooth muscle cells was inhibited by the M2 muscarinic antagonist methoctramine. In lower esophageal sphincter (LES) cells contraction was inhibited by the M3 antagonist p-fluoro-hexa-hydro-sila-difenidol (pF-HSD). Pertussis toxin (PTX) reduced ACh-induced contraction of esophageal but not of LES cells, which suggested that different receptor-linked G proteins are involved. Antibodies against G13 antagonized contraction of esophageal cells and G9-G11 antibodies antagonized contraction of LES cells. The phosphatidylinositol-specific phospholipase C (PLC) inhibitors, U-73122 and neomycin, reduced ACh-induced contraction of LES but not of esophageal cells. Conversely, propranolol and p-chloromercuribenzoic acid (pCMB), which inhibit a phosphatidylcholine-specific phospholipase D (PLD)-dependent pathway, reduced contraction of esophageal but not of LES muscle cells. At 1 and 5 sec after the administration of ACh (10(-5) M), inositol 1,4,5-trisphosphate (IP3) increased only in LES muscle, which suggested that contraction results from PLC-induced IP3 production in the LES but not in the esophagus. The IP3 receptor antagonist heparin, and depletion of intracellular Ca++ stores by thapsigargin or A23187, inhibited ACh-induced contraction of LES but not of esophageal muscle. It was concluded that ACh-induced esophageal contraction depends preferentially on M2 receptors, a PTX-sensitive G13 protein, phosphatidylcholine-specific PLD and production of diacylglycerol (DAG) and is independent of IP3 formation and the release of intracellular Ca++. Conversely, LES contraction is mediated through M3 receptors, a PTX-insensitive G9-G11 protein, activation of PLC, IP3 formation and the release of intracellular Ca++.

Acetylcholine↗
PubMed1992

Acute experimental esophagitis impairs signal transduction in cat lower esophageal sphincter circular muscle.

It has been previously shown that induction of experimental esophagitis in the cat by esophageal perfusion for 30 minutes with 0.1N HCl for 4 consecutive days results in a significant reduction of in vivo lower esophageal sphincter (LES) resting pressure and in vitro spontaneous tone without affecting esophageal response to KCl. It has also been shown that basal LES tone and LES contraction in response to acetylcholine depend on the release of calcium from intercellular stores, whereas esophageal contraction is mediated by extracellular calcium. The present report shows that esophageal acid perfusion impairs the transduction pathway mediating lower esophageal sphincter contraction in response to acetylcholine through release of intracellular calcium because LES strips and single cells no longer contract in response to acetylcholine if calcium is removed from the physiologic salt solution. This suggests that either the intracellular calcium stores or the release mechanisms that mediate maintenance of tone and contraction in response to acetylcholine may be damaged. However, the acid perfusion has no effect on the acetylcholine response in the esophagus, which is mediated by the influx of extracellular calcium. In the LES circular muscle, the injury results in reduced levels of inositol phosphates without affecting resting levels of 5'-cyclic adenosine monophosphate or 5'-cyclic guanosine monophosphate. The reduced levels of 1,4,5-inositol trisphosphate are consistent with impairment in the mechanisms responsible for release of intracellular calcium, although concurrent damage to calcium stores may also occur.

Acute Disease↗
PubMed1992

Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study.

Two hundred thirty patients with reflux symptoms and endoscopically proven erosive esophagitis were enrolled from 15 U.S. centers into a randomized, double-blind, dose-ranging study comparing placebo with omeprazole, 20 or 40 mg given once daily in the morning. Esophagitis grade 2 was present in 44% of patients, grade 3 in 37% of patients, and grade 4 in 19% of patients. Endpoints, defined as complete relief of heartburn and complete esophageal mucosal healing, were assessed after 4 and 8 weeks of treatment. Both omeprazole doses were significantly superior to placebo in complete endoscopic healing. After 8 weeks of treatment, 73.5% of patients in the 20-mg omeprazole group and 74.7% in the 40-mg omeprazole group, compared with 14.0% in the placebo group, had complete healing of the esophageal mucosa. At the end of the study, complete relief of daytime heartburn was obtained in 79.5% of patients in the 20-mg omeprazole group, 81.6% in the 40-mg omeprazole group, and 37.2% in the placebo group (P less than or equal to 0.05). Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05). The median time to complete relief of daytime and nighttime heartburn occurred earlier in the 40-mg group than in the 20-mg group (9 vs. 17 days and 9 vs. 20 days, respectively); however, these differences were not statistically significant. Relief of acid regurgitation and dysphagia also occurred earlier in the 40-mg group. Omeprazole was well tolerated in this group of patients. No unexpected adverse experiences occurred. The results of this study confirm those of six multicenter, international trials in which omeprazole in doses of 20-60 mg provided a degree of esophageal mucosal healing and complete relief of reflux symptoms superior to any other medical treatment.

Adult↗
PubMed1990

VIP-induced alterations in cAMP and inositol phosphates in the lower esophageal sphincter.

Adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and inositol phosphate (IP) levels were measured in thin tissue samples from the circular smooth muscle of the cat lower esophageal sphincter (LES) at 37 degrees C during vasoactive intestinal peptide (VIP)-induced relaxation. On exposure of in vitro LES circular muscle strips to 10(-6) M VIP at the same temperature, relaxation of spontaneous resting tone begins within 3-6 s, is half maximal at 30 s, and maximal at 1 min. VIP-induced changes in cAMP, cGMP, and IP metabolite levels were measured at 5 and 30 s after the addition of 10(-6) M VIP. At 5 s cAMP levels increased significantly with respect to time-matched unstimulated controls, whereas inositol 1,4,5-trisphosphate (1,4,5-IP3) decreased and these changes remained constant at 30 s. cGMP levels were unchanged at either 5 or 30 s after exposure to 10(-6) M VIP. These data suggest that VIP-induced relaxation is temporally linked to decreased 1,4,5-IP3 as well as increased cAMP levels.

Animals↗
PubMed1989

Gallbladder contraction in patients with pigment and cholesterol stones.

Thirty gallbladders were studied in vitro; 5 had black pigment stones and 25 contained manifestations of excess cholesterol in bile. Of the 25, 14 had cholesterol stones, 7 had macroscopic cholesterolosis, and 4 had cholesterol crystals. There were no differences in basal active tension among these groups, but the force of spontaneous phasic contractions was reduced in gallbladders with cholesterol stones, cholesterolosis, and cholesterol crystals compared with specimens with pigment stones (p less than 0.001). The forces developed in response to cholecystokinin-8 (10(-10)-10(-6) M), acetylcholine (10(-7)-10(-3) M), and potassium chloride (20-60 mM) were greater in strips from specimens with pigment stones than in strips from specimens with cholesterol stones or cholesterolosis (p less than 0.001). In cholesterol stones and cholesterolosis specimens, relatively strong muscle strips had similar responses to 10(-6) M cholecystokinin-8 in normal calcium (2.5 mM) and in the absence of extracellular calcium. Weaker muscle strips had a reduced response to cholecystokinin-8 in the absence of extracellular calcium (p less than 0.01). It is concluded that muscle strips exposed to bile with excess cholesterol have a reduced contractility compared with muscle strips from specimens with pigment stones; this impaired contractility precedes gallstone formation, and results from muscle dysfunction.

Adult↗
PubMed1989

Role of peptide histidine isoleucine in relaxation of cat lower esophageal sphincter.

Vasoactive intestinal peptide (VIP) is a candidate as an inhibitory neurotransmitter mediating relaxation of the lower esophageal sphincter (LES) because VIP antiserum reduces LES relaxation in response to neural stimulation. Vasoactive intestinal peptide antiserum, however, does not completely block LES relaxation. Thus it is possible that other neurotransmitters may be involved. Peptide histidine isoleucine has structural homologies with VIP, is synthesized with VIP from a common precursor protein, coexists in some nerve cells, and is coproduced with VIP in some tumors. In numerous organ systems VIP and peptide histidine isoleucine (PHI) produce similar effects, with PHI being less potent than VIP by approximately one log number. In the LES both VIP and PHI produce tetrodotoxin-resistant dose-dependent relaxation, with PHI being almost equipotent with VIP. We therefore tested the hypothesis that PHI may be a second neurotransmitter, partly responsible for relaxation of the cat LES, by using a highly specific rabbit PHI antiserum that exhibits minimal cross-binding with VIP, secretin, and glucagon. In 3 animals, LES and brain tissue were extracted in 0.1 N HCl and assayed with a PHI radioimmunoassay. The antiserum cross-reacted with cat brain and LES showing PHI concentrations greater than 100 ng/g, with the LES containing equal or greater concentrations of PHI than brain tissue. In other animals consecutive LES circular muscle strips were cut, mounted in 1-ml muscle chambers, and stimulated with 6-s square-wave trains of 0.1-, 0.2-, 0.4-, and 0.8-ms pulses at 1, 2, and 5 Hz. These parameters produced relaxation that was completely blocked by tetrodotoxin, and reduced by VIP antiserum, but not affected by adrenergic or cholinergic receptor antagonists. Some strips were incubated in 5% or 10% PHI antiserum, whereas others were incubated in the same concentration of preimmunization serum from the same animal. Incubation in normal serum did not significantly affect relaxation, whereas in the antiserum-treated strips, LES relaxation was reduced by a significant amount (20%-30%) at all parameters of stimulation tested. Incubation in antiserum however had no effect on relaxation induced by VIP (10(-8)-10(-6) M). These data suggest that PHI may play a role in LES relaxation induced by electrical stimulation.

Animals↗
PubMed1989

Calcium sources utilized by cholecystokinin and acetylcholine in the cat gallbladder muscle.

The calcium sources responsible for gallbladder contraction in response to cholecystokinin (CCK) and acetylcholine were studied in vitro in the cat. Sudden replacement of normal physiological salt solution (PSS) with calcium-free PSS blocked the contraction induced by KCl (60 mM) but did not affect the response to CCK (10(-7) M) or acetylcholine (3 x 10(-3) M). Thirty-minute incubation in PSS in which strontium (2.5 mM) was substituted for calcium blocked completely CCK (10(-10) - 10(-6) M)-induced contraction without impairing the response to acetylcholine (10(-7) - 10(-3) M) or KCl (20-80 mM). The contraction induced by acetylcholine (10(-7) - 10(-3) M) was partially blocked by hydroxyverapamil (D-600) (10(-5) M) in normal PSS (Ca 2.5 mm) and was completely blocked by D-600 in strontium (2.5 mm)-containing solution. It is concluded that CCK contracts the gallbladder muscle by mobilizing calcium from intracellular stores, whereas acetylcholine can utilize calcium both from intracellular or extracellular sources.

Acetylcholine↗
PubMed1989

VIP and acetylcholine: neurotransmitters in esophageal circular smooth muscle.

Vasoactive intestinal polypeptide (VIP) and acetylcholine were evaluated as possible inhibitory and excitatory neurotransmitters in the cat esophageal circular smooth muscle. Circular muscle strips 2 mm in thickness were obtained from 1 to 3.4 cm above the lower esophageal sphincter and tested in vitro. Muscle strips contracted with bethanechol (10(-5) M) were relaxed by electrical stimulation (0.5-5 Hz) and by VIP (10(-8)-10(-6) M). Relaxation induced by electrical stimulation was blocked by tetrodotoxin, whereas VIP-induced relaxation was not affected. Highly specific VIP antiserum (5%) antagonized both VIP and electrically induced relaxation, and the antagonism was eliminated when the antiserum was neutralized with VIP (10(-6.5) M). Dopamine (10(-4) M) reduced the relaxation induced both by exogenous VIP and by electrical stimulation but did not affect the relaxation caused by sodium nitroprusside (10(-8)-10(-5) M). In untreated strips, physostigmine (10(-10)-10(-8) M) enhanced the off contraction in response to electrical stimulation, whereas atropine caused a dose-dependent reduction with complete abolition at 10(-4) M. These data suggest that in the esophagus inhibition and excitation are mediated by distinct mechanisms: VIP mediates inhibition and acetylcholine is responsible for the off contraction in response to electrical stimulation.

Acetylcholine↗
PubMed1988

Effects and mechanisms of action of motilin on the cat sphincter of Oddi.

The effects of motilin on gallbladder and sphincter of Oddi motor activity and transphincteric flow were studied in the cat in vivo. Motilin at doses of up to 1 microgram/kg had no effect on gallbladder motility. Increasing doses of intraarterial motilin (32-256 ng/kg) caused an increase in tonic pressures and in the force of phasic contractions of the sphincter of Oddi (p less than 0.001). Simultaneous measurements of myoelectric activity and transphincteric flow showed that motilin caused an increase in the frequency of spike bursts with a concomitant dose-dependent decrease in flow (p less than 0.001). The action of motilin was unaffected by extrinsic denervation (cervical vagotomy or splanchnicectomy), hexamethonium, and propranolol. Atropine, methysergide, or phentolamine partially blocked the excitatory effect of motilin (p less than 0.05), whereas tetrodotoxin, a combination of atropine and methysergide, or naloxone completely blocked its effects (p less than 0.001). It is concluded that (a) motilin decreases sphincter of Oddi flow by increasing its motor activity and (b) motilin activates an intramural excitatory pathway that appears to consist of opiate, serotonergic, and cholinergic neurons.

Ampulla of Vater↗
PubMed1987

Pharmacologic characterization of excitatory and inhibitory cholecystokinin receptors of the cat gallbladder and sphincter of Oddi.

The pharmacologic properties and specificity of cholecystokinin (CCK) receptors of the biliary tract were investigated by testing various sulfated and desulfated CCK fractions and by using specific CCK-gastrin antagonists. Sulfated CCK-7 (5-80 pmol/kg) caused gallbladder contraction and sphincter of Oddi relaxation. Denervation with tetrodotoxin decreased the gallbladder response by 50% and changed the sphincter of Oddi response from relaxation to contraction. Desulfated CCK-7 (80-400 pmol/kg) caused a weak gallbladder contraction that was unaffected by tetrodotoxin. The gallbladder did not respond to CCK-3 (10-80 nmol/kg) or to CCK-2 (10-160 nmol/kg) in doses that completely relaxed the sphincter of Oddi. These doses, however, were 5-2000 times higher than the maximal dose of sulfated CCK-7. After denervation with tetrodotoxin, desulfated CCK-7 (10-400 pmol/kg) induced a weak sphincter of Oddi contraction even with doses five times greater than the maximal dose of sulfated CCK-7. The denervated sphincter of Oddi did not respond to CCK-3 (10-80 nmol/kg) or CCK-2 (10-160 nmol/kg). Furthermore, a continuous proglumide infusion (5-20 mg/kg X min) and bolus doses of dibutyryl cyclic guanosine monophosphate (250-1000 micrograms/kg) blocked the effect of sulfated CCK-8 on the gallbladder and sphincter of Oddi. Higher doses of these antagonists were needed, however, to block the CCK effect on the sphincter of Oddi than on the gallbladder. In contrast, high doses of desulfated CCK-7 (100 pmol/kg) or CCK-3 (200 nmol/kg) did not antagonize the effect of sulfated CCK-8 (10-80 pmol/kg) on the gallbladder. These findings suggest the existence of three sets of specific CCK receptors with molecular configuration requirements determined by the type of cell where these receptors are located: on the postganglionic cholinergic neurons, on the smooth muscle cells of the gallbladder, and sphincter of Oddi, or on the postganglionic noncholinergic, nonadrenergic inhibitory neurons.

Ampulla of Vater↗
PubMed1987

Efficacy of sucralfate in the prevention of recurrence of duodenal ulcers.

Eighty-four patients who were endoscopically confirmed to have healed duodenal ulcers were entered into this 1-year, double-blind, placebo-controlled trial of sucralfate, 1g twice daily, in the prevention of duodenal ulcer recurrence. Patients remained in the study until recurrence of ulceration was endoscopically confirmed. Sixty-one patients could be evaluated for efficacy of treatment. Within 6 months, 23 of 31 placebo patients (74%) and 6 of 30 sucralfate patients (20%) had ulcer recurrence. At 12 months, 25 of 31 placebo patients (80%) and 8 of 30 receiving sucralfate (27%) had ulcer recurrence. The lower rate of ulcer recurrence in patients receiving sucralfate was significant (p = 0.0001). Survival curves also showed that sucralfate was significantly more effective in preventing relapse (p = 0.0001). Three patients were judged as experiencing drug-related side effects, two of which were in the placebo group. The results indicate that sucralfate is significantly more effective than placebo in the prevention of recurrence of duodenal ulcer disease.

Clinical Trials as Topic↗
PubMed1986

The role of the lower esophageal sphincter in reflux prevention.

Manometric measurements of the lower esophageal sphincter have shown that a decrease in resting pressures is the major factor in the pathogenesis of gastroesophageal reflux. About one-fourth of patients with reflux esophagitis, however, have LES pressures that overlap with those of controls, suggesting that other factors may also contribute to the development of reflux esophagitis. Among the additional factors that have been postulated as important are the esophageal acid clearance, the resistance of the esophageal squamous epithelium, the concentration of the causative agents (hydrochloric acid, pepsin, and bile salts), and perhaps the rates of gastric emptying. Nevertheless, in addition to the manometric data, there is a large body of evidence based on clinical, pathological, pharmacological, and therapeutic studies that strongly supports the concept that the lower esophageal tone is the required condition for all other secondary factors to play a role in the pathogenesis of reflux esophagitis.

Animals↗
PubMed1985

Vasoactive intestinal peptide: a neurotransmitter for relaxation of the rabbit internal anal sphincter.

The circular smooth muscle of the rabbit internal anal sphincter, tested in vitro, exhibited spontaneous resting tonus and relaxed with neural stimuli of 0.05-0.5-ms duration and 1-10-Hz frequency. The relaxation was abolished by tetrodotoxin (10(-6) M) but not by atropine or propranolol at the same molar concentration, suggesting that the inhibitory neural fibers mediating relaxation are nonadrenergic and noncholinergic. One-hour incubation in physiologic solution containing 8% of rabbit vasoactive intestinal peptide (VIP) antiserum significantly reduced the relaxation induced by electrical stimulation. The reduction was greater for the shorter duration stimuli, ranging from 80% to 50% for 0.05-ms stimuli to 35%-11% for 0.5-ms stimuli. Control strips were relaxed in a dose-dependent fashion by 10(-9)-10(-6) M VIP; the antiserum at the concentration used completely blocked the relaxation produced by 10(-7) M VIP and reduced the relaxation produced by 10(-6) M VIP. Adenosine triphosphate also relaxed the internal anal sphincter in a dose-dependent manner. Prolonged inhibitory nerve stimulation (0.5 ms, 10 Hz, 30-min train) caused significant reduction in the relaxation induced by exogenous VIP, whereas the relaxation induced by adenosine triphosphate was unaffected. These data are consistent with VIP being an inhibitory neurotransmitter responsible for relaxation of the internal anal sphincter.

Adenosine Triphosphate↗
PubMed1984

Vasoactive intestinal polypeptide. A neurotransmitter for lower esophageal sphincter relaxation.

The effect of rabbit vasoactive intestinal polypeptide (VIP) antiserum on in vitro relaxation of the lower esophageal sphincter (LES) was studied in 10 cats. The stomach and esophagus were opened along the lesser curvature of the stomach and stripped of mucosa. Consecutive strips were cut and mounted in a 2.5-ml muscle chamber. They were perfused with Tyrode's solution and oxygenated continuously. After equilibration for 1 h, perfusion was stopped and one strip from the lower esophageal sphincter region was incubated in solution that contained 12-25 parts of VIP antiserum per 1,000 to Tyrode's solution, while a second strip was incubated in a solution of normal rabbit serum at the same concentration. A third strip was maintained in Tyrode's solution for the duration of the experiment. After a 1-h incubation, the strips were stimulated with 6-s square wave trains of 0.1-, 0.2-, 0.4-, and 0.8-ms pulses at 1, 2, and 5 Hz. These stimulation parameters produced LES relaxation that was completely blocked by tetrodotoxin but not by atropine or phentolamine. The strips incubated in Tyrode's solution or in normal serum relaxed reliably and consistently at all levels of stimulation. In the antiserum-treated strips, LES relaxation in response to all stimuli was significantly inhibited. Strips treated with normal serum were relaxed in a dose-dependent fashion by 10(-7) and 10(-6) M VIP, whereas the antiserum inhibited the relaxation induced by 10(-7) M, but not by 10(-6) M, VIP. Stimulation with two successive 15-min trains of electrical pulses (2 ms, 5 Hz) separated by 30 min of rest released increasing amounts of VIP into the bathing solution. VIP released during the second train of electrical stimulation was significantly (P less than 0.05) greater than in control conditions. In the cat LES, VIP antiserum inhibits the relaxation induced by exogenous VIP or by electric stimulation of nonadrenergic, noncholinergic inhibitory nerves at a level that causes the release of VIP. These findings are consistent with the hypothesis that VIP may be an inhibitory neurotransmitter responsible for LES relaxation.

Animals↗