Characteristics of 5-hydroxytryptamine receptors involved in contraction of feline ileal longitudinal smooth muscle

Abstract

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the 5HT(2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron but was inhibited by the 5-HT(1) receptor antagonist methysergide and 5-HT(4) receptor antagonist GR113808. These results indicate that 5-HT(1) and 5-HT(4) receptors may mediate the contraction of the 5-HT-induced response and 5-HT(2) and 5-HT(3) receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.

Keywords: 5-HT; Contraction; Ileum; Longitudinal smooth muscle; Relaxation.

Fig. 1

Representative tracing showing the effect of 5-HT on the spontaneous contraction of feline longitudinal smooth muscle. 5-HT was added cumulatively (10^-10~10^-6 M) with 5-min contact time for each concentration.

Fig. 2

Effect of atropine or guanethidine on 5-HT-induced contraction. Concentration-response curves to 5-HT in the absence (○) and presence of 0.1 #x00B5;M atropine (●) (A) or 1 #x00B5;M guanethidine (■), (B). Preparations were incubated with atropine or guanethidine for 10 min before and during 5-HT treatment. Each point represents the mean±S.E.M. (n=6).

Fig. 3

Effect of TTX on 5-HT-induced contraction. Concentration-response curves to 5-HT in the absence (○) and presence of 0.1 µM (●) and 1 µM (■) TTX. Preparations were incubated with TTX for 10 min before and during 5-HT treatment. Each point represents the mean±S.E.M. (n=5).

Fig. 4

Concentration-response curves for 5-HT- (○, n=11), 5-MOT- (●, n=8) and mosapride- (■, n=10) induced contraction. Each point represents the mean±S.E.M.

Fig. 5

Inhibitory effect of 5-HT receptor antagonists on 5-HT-induced contraction. The preparation was incubated with (A) methysergide (1 µM, n=5), (B) ketanserin (0.1 µM, n=8), (C) ondansetron (1 µM, n=8) or (D) GR113808 (10 nM, n=5) for 30 min before and during 5-HT treatment. Absence (○) or presence (●) of antagonist. Each point represents the mean±S.E.M. ^*p<0.05 and ^**p<0.01 compared to the same concentration of 5-HT-induced contraction alone.

Fig. 6

Major roles of 5-HT receptors in isolated feline ileum longitudinal smooth muscle. 5-HT can stimulate 5-HT₁ or 5-HT₄ receptors resulting in contraction of smooth muscle. 5-HT can also stimulate 5-HT₂ or 5-HT₃ receptors resulting in relaxation of smooth muscle.