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Biomedical subjects

R K Goyal

Publications and source records attributed to R K Goyal.

At least 181 records · Page 10Linked to original sources
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

The inhibitory effect of clonidine on the oestrogen-primed rat isolated uterus.

The investigation was undertaken to study the mechanism of the inhibitory effects of clonidine on the oestrogen-primed rat isolated uterus. Clonidine produced dose-dependent relaxations of the rat isolated uterus which were competitively blocked by yohimbine but not by prazosin. Metiamide, a specific H2-histamine receptor antagonist, inhibited clonidine-induced responses only at a high concentration (1.0 X 10(-6)M). Propranolol, a beta-adrenoreceptor antagonist produced competitive antagonism of the clonidine responses. Like clonidine, noradrenaline also produced dose dependent relaxations of the rat isolated uterus. The responses to noradrenaline were not antagonized by either prazosin or yohimbine but were competitively antagonized by propranolol. The responses to clonidine were significantly inhibited by reserpine pretreatment (5 mg/kg; i.p., 24 h before) whilst responses to noradrenaline were significantly increased by this treatment. It is concluded that clonidine inhibits the uterus via an action on alpha 2-adrenoreceptors and possibly also to a lesser extent on H2-histamine receptors, leading ultimately to release of noradrenaline from endogenous stores which causes relaxation by acting on beta-adrenoreceptors.

Animals↗
PubMed1983

Influence of successive vagal stimulations on contractions in esophageal smooth muscle of opossum.

Studies were performed in anesthetized opossums to investigate the influence of successive vagal stimuli on esophageal contractions. Mechanical activity was recorded manometrically 5 cm above the lower esophageal sphincter. Contractions in the esophagus were evoked by electrical stimuli of 2.5 mA, and 1-ms pulse duration applied to the cervical vagi, at various train durations and frequencies. Paired or multiple stimuli of 1-s train length were also tested at different interstimulus intervals (ISI). Paired stimuli at an ISI of less than or equal to 3 s and at a frequency of less than or equal to 10 Hz showed refractoriness, i.e., the contractions to the first stimulus inhibited the contraction to the second stimulus. A frequency of 50 Hz showed initial inhibition, i.e., the second stimulus inhibited the contraction to the first stimulus. Repetitive stimuli applied at a rate of 8/min (ISI 6.5 s) evoked contractions to each stimulus. At 15/min, every second or third contraction was inhibited. With stimuli applied at 30/min, contractions occurred only in response to the first and/or the last stimulus; depending upon the frequency of vagal stimulation. The intervening stimuli did not evoke any contractions. A long train stimulus produced an initial, a terminal, or both contractions depending on the stimulation value. These studies show that (a) vagal efferent stimulation causes initial inhibition and refractoriness in the esophageal smooth muscle; (b) the degree of initial inhibition increases with increasing frequency of stimulation; (c) the occurrence of contractions only at the onset and the end of a long train stimulus may be due to the influence of initial inhibition and refractoriness.

Animals↗
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↗
PubMed1982

Mechanism of action of histamine in the estrogen-primed rat uterus.

Histamine produced a dose-dependent relaxation of uterine strips obtained from the estrogen-primed rat uterus. The responses to histamine were blocked competitively by metiamide (10(-8)-10(-8) M), a specific H2-receptor antagonist. Propranolol, a selective beta-receptor blocker also produced competitive antagonism of the responses to histamine in the same dose range (10(-8)-10(-6) M). The pA2 value obtained for metiamide (8.9) was not significantly different from that obtained for propranolol (8.6). Nialamide (2.2 X 10(-6) M), the monoamine oxidase inhibitor, and cocaine (4.3 X 10(-6) M), the selective noradrenaline uptake blocker, potentiated the responses to histamine. However bretylium (2.4 X 10(-5) M), and adrenergic neuron blocker inhibited the responses to histamine. The combined effect of tyramine and histamine was found to be additive. Our data suggest that the histamine-induced relaxation of rat uterus may be produced through the stimulation of presynaptic H2-receptors which causes the release of noradrenaline. The released noradrenaline acts on the postsynaptic beta-receptors and produces relaxation of the rat uterus.

Animals↗
PubMed1982

A computer-assisted technique for 24-hour esophageal monitoring.

Modern computer design offers the opportunity to rapidly and objectively analyze the large quantity of data obtained during prolonged intraesophageal monitoring. The purpose of this study is: (1) to describe a rapid automated technique for acquisition and analysis of esophageal parameters, using a microcomputer; and (2) to compare computerized versus manual analysis of physiograph recordings. Ten normal subjects underwent 24-hr computerized monitoring of intraesophageal function, including: (1) pH recording at 5 and 10 cm above the lower esophageal sphincter (LES); (2) pharyngeal contraction; (3) esophageal contraction at 5 and 10 cm; (4) posteriorly directed LES pressures; and (5) gastric pressure. Segments from several studies were chosen for comparison of physiograph data with that obtained by computer. No significant differences were found except for the number of esophageal contractile events. This difference stems from a problem of shifting baseline related to subject position. Thus, the computer can be used for analysis of large quantities of data obtained from prolonged esophageal monitoring.

Computers↗