Characterization of the 5-hydroxytryptamine receptors mediating contraction in the intestine of Suncus murinus.
1. The effects of 5-HT and 5-HT agonists to induce contraction and the 5-HT receptors mediating these effects were investigated in the proximal, central and terminal intestinal segments of Suncus murinus. 2. The contraction curves to 5-HT (3 nM - 30 microM) were shifted to the right by methysergide (1 microM) and ritanserin (0.1 microM), without affecting the maximum response. 3. In the central and terminal segments (but not the proximal segments) ondansetron (1 microM) and atropine (1 microM) significantly attenuated the contractions to higher concentrations of 5-HT. The selective 5-HT4 receptor antagonist SB204070 (1 nM), failed to modify 5-HT induced contractions in any segment examined. 4. 5-carboxamidotryptamine, alpha-methyl-5-HT and 5-methoxytryptamine (0.003 - 3.0 microM) induced contractions but unlike 5-HT, higher concentrations of these three agents failed to increase the response or were associated with a decrease in response. 2-methyl-5-HT (0.03 - 1.0 microM) was ten times less potent than 5-HT to induce contraction but achieved the same maximum response. 5. The contractions induced by the lower concentrations of 2-methyl-5-HT (0.03 - 1.0 microM) in all segments were markedly reduced or abolished by methysergide (1.0 microM); the response to the higher concentrations of 2-methyl-5-HT (3 - 30.0 microM) were markedly reduced by atropine (1.0 microM) and ondansetron (1.0 microM). 6. In all segments examined, tetrodotoxin (1 microM) significantly reduced the 5-HT-induced contraction. 7. It is concluded that the 5-HT-induced contraction was mediated via 5-HT2 (ritanserin sensitive) receptors in all regions of the intestine, with 5-HT3 (ondansetron sensitive) receptors mediating an additional major component in the central and terminal regions.
Javid
F A
FA
Postgraduate Studies in Pharmacology, The School of Pharmacy, University of Bradford, Bradford BD7 1DP.
Naylor
R J
RJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005260:Female; D007422:Intestines / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012788:Shrews
D018727:Muscarinic Antagonists; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D001285:Atropine