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S Rattan

Publications and source records attributed to S Rattan.

At least 91 records · Page 5Linked to original sources
PubMed1986

The non-adrenergic non-cholinergic innervation of the esophagus and the lower esophageal sphincter.

Electrical stimulation of the vagus nerve causes the relaxation of the lower esophageal sphincter (LES), followed by the sequential contraction of the esophageal body smooth muscle. These responses are similar to those in response to swallowing. The nature of the inhibitory neurotransmitter responsible for the LES relaxation is not exactly known. Following the preliminary criteria, we systematically examined the possibility of different candidate substances as the inhibitory neurotransmitter. We ruled out the role of different neurotransmitter substances including the cholinergic and adrenergic ones. Finally, we examined the possibility of VIP as the inhibitory neurotransmitter of non-adrenergic non-cholinergic intramural neurons of the LES, responsible for LES relaxation. VIP caused relaxation of the LES by its action directly at the muscle. VIP antiserum, which antagonized the action of VIP, caused a significant antagonism of LES relaxation caused by vagal stimulation and local stimulation. These results suggest that VIP acts as an inhibitory neurotransmitter for LES relaxation. The exact nature of the neurotransmitter responsible for the esophageal peristalsis is also not known. It is suggested that the contraction of the longitudinal smooth muscle of the esophagus is mediated by acetylcholine and substance P, while the circular smooth muscle contraction is mediated through the release of acetylcholine and an unknown non-adrenergic non-cholinergic neurotransmitter. Whether the latter neurotransmitter is VIP remains to be seen.

Animals↗
PubMed1984

Mechanical and electrical activity of esophageal smooth muscle during peristalsis.

Mechanical events and membrane potential changes in response to evoked swallows and cervical vagal stimulation (10 and 40 Hz) were recorded in anesthetized opossums. Miniature strain-gauge transducers monitored the mechanical activity of the two layers. A suction electrode recorded from the intact esophagus, from a proximally based pedicle flap of longitudinal muscle (LM), and from circular muscle (CM). The onset of swallowing was marked by the onset of mylohyoid activity. During swallows LM contraction preceded CM contraction and was of longer duration. The latencies of LM and CM contraction were 1,980 +/- 38 and 2,250 +/- 101 ms, respectively. The durations of contraction of LM and CM were 5,590 +/- 260 and 3,330 +/- 67 ms, respectively. LM showed no hyperpolarization but showed depolarization and spike burst. The CM showed prompt hyperpolarization followed by depolarization and spike burst. Responses to vagal stimulation were qualitatively similar to swallows. The different components of the responses were quantitatively modified by changes in stimulus frequency. These studies show that, during peristalsis in response to swallows and vagal stimulation, 1) LM contraction occurs before CM and is of longer duration, and 2) unlike CM, LM does not hyperpolarize prior to depolarization.

Animals↗
PubMed1984

Swallowing induces sequential activation of esophageal longitudinal smooth muscle.

We examined the mechanical activity of the longitudinal and circular muscles of the esophagus at three different levels (9, 5, and 1 cm above the lower esophageal sphincter) during peristalsis induced by swallows or vagal stimulation in anesthetized opossums with miniature strain gauges applied in the axis of muscle fibers. The onset of longitudinal muscle contraction occurred in an aboral sequence with swallows but simultaneously with vagal stimulation. The speed of longitudinal muscle activation with swallows was 7.6 +/- 1.7 cm/s. Circular muscle contraction occurred in an aboral sequence with vagal stimulation and swallowing with speeds of 4.1 +/- 0.8 and 2.3 +/- 0.1 cm/s, respectively. Longitudinal muscle contracted before the circular muscle at all sites. The duration of longitudinal muscle contraction increased aborally (P less than 0.05) with swallowing or vagal stimulation. These studies show that 1) during swallowing, esophageal longitudinal and circular smooth muscle contract in a sequential fashion, 2) the longitudinal muscle sequential contraction is due to central mechanisms, whereas circular muscle sequential contraction may be due to both central and peripheral mechanisms, and 3) peripheral neuromuscular mechanisms produce regional differences in the duration of longitudinal muscle contraction.

Animals↗
PubMed1984

Pharmacologic identification, activation and antagonism of two muscarine receptor subtypes in the lower esophageal sphincter.

Lower esophageal sphincter pressures were monitored with water-filled catheters in anesthetized opossums. Muscarinic agonists McN-A-343 and bethanechol were administered in the arterial supply of the sphincter. McN-A-343 caused relaxation after a brief contraction of the sphincter. Bethanechol caused a dose-dependent contraction. Tetrodotoxin antagonized the inhibitory effect of McN-A-343 but did not antagonized sphincter contraction caused by McN-A-343 or bethanechol. The mean ED50 values were 6.9 nmol/kg i.a. for McN-A-343-induced relaxation, 10.5 nmol/kg i.a. for McN-A-343-induced contraction and 0.4 nmol/kg i.a. for bethanechol-induced contraction. Atropine caused a dose-dependent rightward shift in the dose-response curves of inhibitory and excitatory effects of the two muscarinic agonists. Pirenzepine caused a dose-dependent rightward shift in the dose-response curves of McN-A-343-induced relaxation. Pirenzepine did not modify sphincter contraction caused by the muscarinic agonists. 4-Diphenylacetoxy-N-methylpiperidine methiodide, on the other hand, did not modify McN-A-343-induced sphincter relaxation but caused dose-dependent rightward shifts in the dose-response curves of sphincter contraction caused by McN-A-343 or bethanechol. These studies suggest that there are two distinct types of muscarine receptors in the opossum lower esophageal sphincter. The M1 muscarine receptors are present on the inhibitory neurons and participate in the synaptic transmission between vagal preganglionic and intramural postganglionic inhibitory neurons. They are activated by McN-A-343 and antagonized by pirenzepine. The M2 muscarine receptors are located directly on the sphincter muscle. They are also activated by McN-A-343, but are selectively activated by bethanechol and are antagonized by 4-diphenylacetoxy-N-methylpiperidine methiodide.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1983

Membrane potential and mechanical responses of the opossum esophagus to vagal stimulation and swallowing.

Studies were performed in anesthetized opossums. The electrical changes, recorded using a suction electrode applied to the outside of the esophagus, and mechanical activity, recorded by an intraluminal catheter, were monitored from 5 cm above the lower esophageal sphincter. Swallowing was associated with membrane hyperpolarization followed by depolarization and spike burst. Electrical stimulation of the decentralized vagus also caused a prompt hyperpolarization followed by an overshoot depolarization. Single pulses of stimulation caused primarily hyperpolarization. The amplitude and duration of hyperpolarization increased with increasing frequencies of vagal stimulation. Spike burst occurred as the membrane potential was recovering from the peak hyperpolarization and moving toward peak depolarization. The latency of onset of spike burst decreased with increasing frequency of vagal stimulation. The muscle contraction occurred after a latency. The latency of contractions, like the latency of spike burst, decreased with increased frequency of vagal stimulation. These studies show that (a) membrane hyperpolarization is present during the latent period of contraction associated with swallowing, suggesting that swallow-induced esophageal response may be mediated by vagal inhibitory pathway to the esophagus and (b) spike bursts can be temporally dissociated from depolarization by changing the vagal stimulation frequency, suggesting that spike burst and depolarization may be mediated by different excitatory mechanisms.

Animals↗
PubMed1982

Vasoactive intestinal peptide causes peristaltic contractions in the esophageal body.

Vasoactive intestinal peptide (VIP) caused a dose-dependent fall in lower esophageal sphincter (LES) pressure and dose-dependent contractions in the body of the esophagus. The response to VIP in the esophagus or LES was not modified by atropine, phentolamine, haloperidol, pyrilamine, methysergide, indomethacin and tetrodotoxin, showing that is exerts direct action at the esophageal smooth muscle. These studies suggest that VIP causes contraction in the esophageal body and relaxation of the LES by a direct action on the smooth muscle. It is possible that VIP may be the common mediator of noncholinergic, nonadrenergic neurons that cause relaxation of the lower esophageal sphincter and contraction in the esophageal body.

Animals↗
PubMed1980

VIP as a possible neurotransmitter of non-cholinergic non-adrenergic inhibitory neurones.

Many peripheral autonomic nerves are neither cholinergic nor adrenergic. Such nerves are widely distributed in the gastrointestinal, urogenital and respiratory tracts, and in blood vessels. The nature of their neurotransmitter is not known. We have previously reported that vasoactive intestinal polypeptide (VIP) is a potent inhibitor of opossum lower oesophageal sphincter (LOS) and that its inhibitory effect is exerted directly on the sphincter muscle. Subsequent studies have confirmed the inhibitory effect of VIP on LOS in other species. Recently, very high tissue levels of VIP have been reported in the LOS and other gastrointestinal sphincters. Furthermore, VIP has been localized to intramural neurones and is released upon electrical stimulation of the vagus nerve. We report here that immunoantagonism of VIP with a high-titre antiserum antagonized inhibitory neuromuscular transmission in the LOS. These findings provide evidence of a role for VIP as an inhibitory neurotransmitter.

Animals↗
PubMed1980

Effects of sodium nitroprusside and verapamil on lower esophageal sphincter.

Infusions of verapamil (V) and sodium nitroprusside (NP) caused dose-dependent reductions in the lower esophageal sphincter pressure (LESP) in anesthetized opossums. Verapamil caused a gradual fall during the infusion and a gradual recovery upon cessation of the infusion. On the other hand, NP caused a prompt reduction and a prompt recovery. Both the agents also caused a fall in arterial blood pressure, but the fall in LESP was not related to the fall in the blood pressure. Both the agents antagonized the tonic and the phasic components of the LESP and, in large doses, both drugs almost abolished the LESP. Esophageal contractions were also antagonized by both agents, although verapamil was more effective than nitroprusside in this regard. These studies show that phasic and tonic components of LESP are not related to distinctive verapamil and nitroprusside sensitive calcium activation systems. Moreover, the V- and NP-sensitive calcium activation systems may lie in series rather than parallel.

Animals↗
PubMed1980

Evidence against purinergic inhibitory nerves in the vagal pathway to the opossum lower esophageal sphincter.

Studies were performed on anesthetized opossums. Lower esophageal sphincter pressures were measured with waterfilled and continously perfused catheters anchored in the sphincter. Administration of adenosine 5'-triphosphate (ATP) and ADP in the left gastric artery usually produced an initial contraction followed by a more prolonged inhibition. Adenosine, on the other hand, produced only inhibition. The effect of ATP was not modified by phentolamine (1 mg/kg), propranolol (1 mg/kg) or atropine (30 micrograms/kg). Tetrodotoxin partially antagonized (P less than 0.05) the inhibitory effects of ATP and adenosine, but augmented the excitatory effect of ATP (P less than 0.05). 2-2'-Pyridylisatogen tosylate selectively antagonized the effects of ATP without modifying the effect of adenosine. This antagonist, however, did not modify the resting sphincter pressure or the vagal stimulated sphincter relaxation. Dipyridamole enhanced the inhibitory effect of adenosine, but did not augment vagal stimulates sphincter relaxation. There was no cross-tachyphylaxis between ATP and adenosine. Tachyphylaxis, either to ATP or adenosine, did not inhibit the vagal stimulated sphincter relaxation. These studies show that: (a) ATP and adenosine may act on different receptor sites to modify sphincter pressure; (b) only a small part of the inhibitory effect of ATP and adenosine is mediated by the inhibitory neurons; (c) neither ATP nor adenosine appears to be the inhibitory transmitter released by the noncholinergic, nonadrenergic inhibitory neurons in the vagal pathway to the lower esophageal sphincter.

Adenosine↗
PubMed1978

Evidence of 5-HT participation in vagal inhibitory pathway to opossum LES.

Studies were performed in anesthetized opossums to investigate the nature of vagal-stimulated sphincter relaxation, which is resistant to antagonism by a combination of hexamethonium and atropine. The sphincter pressures were measured with water-filled and continuously perfused catheters anchored in the lower esophageal sphincter. Neither increase in the doses of hexamethonium and atropine nor addition of diphenhydramine further modified the vagal response. However, administration of 5-methoxydimethyltryptamine in the presence of hexamethonium and atropine abolished vagally stimulated sphincter relaxation. In animals pretreated with parachlorophenylalanine, addition of atropine and hexamethonium also abolished vagally stimulated sphincter relaxation. In the experiments in which lower esophageal sphincter relaxation on vagal stimulation was abolished, the local stimulation of intramural neurons still produced normal lower esophageal sphincter relaxation. These studies suggest that 5-hydroxytryptamine may participate in the vagal inhibitory pathway to the lower esophageal sphincter.

Animals↗
PubMed1977

Effects of 5-hydroxytryptamine on the lower esophageal sphincter in vivo: evidence for multiple sites of action.

Intravenous administration of 5-hydroxytryptamine (5-HT) caused a dose-dependent contraction in the lower esophageal sphincter in the opossum. The smallest dose of 5-HT which caused a detectable contraction of the sphincter was 0.5 mug/kg, and a maximal sphincter contraction was produced by a dose of 40 mug/kg. Methysergide converted the contractile effect of 5-HT to a dose-dependent fall in the sphincter pressure; maximal inhibition of 77.2 +/- 7.2% of the resting pressure occurred with a dose of 40 mug/kg. The inhibitory effect of 5-HT was antagonized by tetrodotoxin, 5 MeO-DMT, and 5-HT tachyphylaxis. 5 MeO-DMT enhanced 5-HT-induced contraction of the sphincter. In the presence of 5 MeO-DMT and methysergide, 5-HT still caused a brief contraction of the sphincter; this contraction appeared to be due to stimulation of postganglionic cholinergic neurons as it was antagonized by tetrodotoxin or atropine. Reserpinization caused enhancement of the sphincter contraction by 5-HT. In the reserpinized animals in the presence of methysergide, 5-HT caused a small initial contraction followed by prolonged inhibition; atropine antagonized the initial contraction, while inhibition was antagonized by 5 MeO-DMT. These studies are consistent with the view that 5-HT exerts several different effects on the sphincter. 5-HT causes contraction of the sphincter by its direct action on the muscle and also by stimulation of cholinergic excitatory neurons. In addition, 5-HT inhibits the sphincter by stimulation of nonadrenergic inhibitory neurons.

5-Methoxytryptamine↗
PubMed1976

The mechanism of action of gastrin on the lower esophageal sphincter.

Gastrin I or pentagastrin caused contraction of the lowe esophageal sphincter in anesthetized oppossums. The contraction was not modified, either qualitatively or quantitatively, by 30 or 1000 mug per kg atropine pretreatment. Moreover, neural block with tetrodotoxin did not influence the effect of gastrin on the sphincter pressure. H2 receptor antagonist, metiamide, did not modify the magnitude of the contractile response of the lower esophageal sphincter to gastrin I. These studies show: a) gastrin does not cause sphincter contraction by stimulating cholinergic neurons: and b) gastrin does not exert an inhibitory effect on the sponcter pressure by stimulating H2 receptors. We suggest that gastrin may contract the lower esophageal sphincter by a direct action on the sphincter muscle.

Animals↗