5-Methoxytryptamine and 2-methyl-5-hydroxytryptamine-induced desensitization as a discriminative tool for the 5-HT3 and putative 5-HT4 receptors in guinea pig ileum

  title={5-Methoxytryptamine and 2-methyl-5-hydroxytryptamine-induced desensitization as a discriminative tool for the 5-HT3 and putative 5-HT4 receptors in guinea pig ileum},
  author={Douglas A Craig and R. M. Eglen and L. K. M. Walsh and L. A. Perkins and Roger Lewis Whiting and David E. Clarke},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  • D. Craig, R. Eglen, D. Clarke
  • Published 1 July 1990
  • Biology, Chemistry
  • Naunyn-Schmiedeberg's Archives of Pharmacology
SummaryAgonist-induced desensitization has been utilized to discriminate and independently “isolate” the neuronal excitatory receptors to 5-hydroxytryptamine (5-HT) in the guinea pig ileum (5-HT3 and putative 5-HT4 receptors). Electrically stimulated longitudinal muscle myenteric plexus preparations, and non-stimulated segments of whole ileum were used. Exposure to 5-methoxytryptamine (10 μmol/l) inhibited completely responses to 5-HT at the putative 5-HT4 receptor without affecting 5-HT3… 
fnvolves Several 5-HydroxytryptarnincRecept6r Subtypes
5-HT-induced jejunal secretion involves more than one 5-HT receptor subtype, with both neural and non-neural mechanisms contributing to the response.
SDZ 205-557, a selective, surmountable antagonist for 5-HT4 receptors in the isolated guinea pig ileum
It is concluded that SDZ 205-557 is a potent, selective and surmountable antagonist at 5- HT4 receptors in the isolated guinea pig ileum, and is a more practical tool for the characterization of 5-HT4 receptors than ICS 205-930.
Changes in sensitivity of 5-HT receptor mediated functional responses in the rat oesophagus, fundus and jejunum following chronic infusion with 5-hydroxytryptamine
It is shown in a preliminary characterisation that in rat jejunum, 5-HT produces a biphasic concentration-effect curve which is mediated by a putative 5-ht7/5-HT3 receptor-mediated responses in rat oesophagus, fundus andJejunum respectively when measured in vitro.
Effects of 5-HT4 receptor stimulation on basal and electrically evoked release of acetylcholine from guinea-pig myenteric plexus
5-methoxytryptamine may both inhibit (via 5-HT1 receptors) and facilitate (via5-HT4 receptors) the evoked release of acetylcholine from guinea-pig myenteric neurones and the facilitatory action is unmasked when the 5- HT1 receptor is blocked by methiothepine.
5-Hydroxytryptamine (5-HT) Cellular Sequestration during Chronic Exposure Delays 5-HT3 Receptor Resensitization due to Its Subsequent Release*
The findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization in the guinea pig ileum.
5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae
Concentration-effect curves to 5-HT were not affected by tetrodotoxin or indomethacin, sugesting that 5- HT-induced relaxation of the tunica muscularis mucosae was mediated via a postjunctional receptor, independent of endogenous prostanoids.
Cisapride and a structural analogue, R 76186, are 5-hydroxytryptamine4 (5-HT4) receptor agonists on the guinea-pig colon ascendens
Both cisapride and R 76186 mediate their contractile effects in the guinea-pig colon ascendens through agonism at the 5-HT4 receptor, though cisap Ride also uses a non-5-HT mechanism.
Comparison of 5-HT4 receptors in guinea-pig colon and rat oesophagus: effects of novel agonists and antagonists
Abstract5-HT4 receptors in isolated distal colon myenteric plexus of guinea-pig, mediating contraction of longitudinal smooth muscle, have been further characterized by selective agonists and
Investigation of the 5-hydroxytryptamine receptor mediating the “transient” short-circuit current response in guinea-pig ileal mucosa
The data show that neuronal and non-neuronal 5-HT receptors are involved in the regulation of secretion in ileal mucosa, and propose the presence of a neuronal 5- HT4 receptor located upstream of the well characterized neuronal 3-methyl-5-hydroxytryptamine receptors to be responsible for the high potency5-HT response.


Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine receptor.
  • D. Craig, D. Clarke
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1990
Unlike Gaddum's M receptor, the putative 5-HT4 [corrected] receptor site exhibits a higher sensitivity to agonism by 5- HT and is resistant to antagonism by cocaine.
A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system.
The relatively low affinity of this hippocampal receptor for 5-CT, its stimulation by RU 28253 but not by RU 24969, and its previously reported pharmacological characteristics support the contention that this 5- HT receptor and the 5-HT receptor of mouse embryo colliculi neurons in primary culture present great homologies.
Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites
In rat brain cortex slices preincubated with [3H]5-HT, the evidence indicates that the presynaptic 5- HT autoreceptor belongs to the 5-HT1B receptor subtype.
Receptors for 5-hydroxytryptamine on the sympathetic nerves of the rabbit heart
Summary1.The Langendorff perfused rabbit heart has been used to investigate the effects of 5-hydroxytryptamine (5-HT) and several closely related analogues as stimulants and inhibitors of transmitter
Unsurmountable antagonism to 5-hydroxytryptamine in rat kidney results from pseudoirreversible inhibition rather than multiple receptors or allosteric receptor modulation.
Pseudoirreversible antagonism, over allosteric receptor modulation, offers an explanation that does not involve the postulation of allosterics effector sites or changes in the state of the 5-HT2 receptor.
The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons
It is reported that this non-classical 5-HT receptor can be stimulated by 4-amino-5-chloro-2-methoxy substituted benzamide derivatives and is similar to the pharmacology of the high affinity 5- HT receptors involved in the indirect stimulation of smooth muscle in the guinea pig ileum.
Neuronal 5-HT receptors in the periphery
  • J. Fozard
  • Biology, Chemistry
  • 1984
Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron).