Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The selective 5-HT3 receptor antagonist, ICS 205-930 (Sandoz), has potent effects on gastrointestinal motor activity in vitro and in vivo. This double-blind, crossover study compared the effects of 20 mg of ICS 205-930 infused intravenously with those of a placebo on the motor activity of the oesophageal body and the lower oesophageal sphincter (LOS). Each of twelve healthy young men participated in two recording sessions one week apart. Oesophageal pressures were recorded using a catheter assembly with orifices 2, 5, 8, 11, and 14 cm above the oral border of the LOS and a Dent sleeve for measurement within the LOS. During and after the infusion of ICS 205-930, amplitude and duration of swallow-initiated contractions in the smooth muscle oesophagus increased slightly, the area under the curve as a measure of contraction strength being significantly greater than after placebo (P less than 0.05). LOS resting pressure increased slightly during ICS 205-930 infusion and was significantly higher than it was in the case of the placebo (P less than 0.001). Propagation velocity of contractions, incidence of tertiary contractions and relaxation of LOS upon swallowing remained unaffected. ICS 205-930 was well tolerated. It is concluded that ICS 205-930 has slight but distinct stimulatory effects on contraction strength in the smooth muscle oesophagus and LOS resting pressure.
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PMID:Effects of the 5-HT3 receptor antagonist, ICS 205-930, on oesophageal motor activity and on lower oesophageal sphincter pressure: a double-blind cross-over study. 208 22

Peripheral 5-HT3 receptor mechanisms are involved in activation of gastrointestinal (GI) mucosal vagal afferent fibres. 5-HT3 receptor mechanisms in the central nervous system (CNS) may be involved in behavioural and reflex motility responses. This study investigates the processing of different sensory inputs in the CNS and the involvement of 5-HT3 receptors at these different levels. In Urethane (1.5 g/kg, i.p.) anaesthetized, splanchnectomized ferrets, the jugular vein was cannulated for intravenous (i.v.) drug injection, and the coeliac axis for intraarterial (i.a.) injection close to the upper GI tract. The carotid artery was intubated with a T-cannula for CNS-directed intracarotid (i.c.) injections. An intragastric cannula was used for fluid distension (40-50 ml), and an oesophageal catheter for balloon distension (2 ml). Efferent fibres were dissected from the right cervical vagus for single-unit recording. Nineteen single vagal efferent fibres were selected, with low frequency resting discharge (2.5 +/- 0.3 impulses/s), but no respiratory or cardiovascular phasic input. All responded rapidly (< 2.5 s) to gastric distension (532 +/- 230% change in firing rate) and oesophageal distension (300 +/- 170%). Gastric distension caused excitation in 14 fibres, inhibition in 4 fibres, and a biphasic response in 1. Oesophageal distension excited 16 and inhibited 3. Discharge was also influenced by i.a. injection of 5-HT or the 5-HT3 receptor agonist 2-methyl 5-HT (10-100 micrograms) in all fibres tested. These responses consisted of rapid (< 2.5 s) and powerful changes in firing rate, with excitation, inhibition or biphasic responses. 65% of responses to i.c. or i.v. injection were opposite in direction to those after close i.a. injection, indicating the activation of a different population of receptors. No differences were seen between effects of i.c. and i.v. injections. The 5-HT3 receptor antagonist granisetron (100 micrograms/kg, i.v.) blocked or reduced efferent responses to 5-HT receptor agonists, whereas responses to gastric and oesophageal distension were unchanged. Thus there is extensive convergence of inputs from gastric and oesophageal mechanoreceptors onto vagal motorneurones. These central effects of mechanical stimuli do not involve 5-HT3 receptor mechanisms. Other 5-HT3 receptor inputs are evident, probably peripherally from GI mucosal afferent fibres and from within the CNS.
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PMID:Gastro-oesophageal afferent and serotonergic inputs to vagal efferent neurones. 780 70