Contractile Responses of Longitudinal Muscle Strip to 5-HT and Influences of Divalent Cations in the Guinea-Pig Isolated Colon.

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The contractile effects of 5-hydroxytryptamine (5-HT) and influences of several kinds of divalent cations were investigated on longitudinal muscle strips of the guinea-pig isolated distal colon. 5-HT (10nM-10μM) produced phasic contractions which were partially inhibited by atropine (1μM) and markedly inhibited by tetrodotoxin (1μM), indicating that 5-HT acts mainly on the myenteric plexus and releases transmitters to cause contraction of the longitudinal muscle. The contractile response to 5-HT (3μM) was almost completely inhibited by spantide (10μM), a substance P antagonist, in the presence of atropine (1μM), while spantide alone did not block 5-HT-induced contraction. Of several divalent cations including Cd2+, Co2+, Mg2+, Mn2+, Ni2+, Sr2+ and Zn2+, Cd2+ ions (10μ-100μM), which block L-and N-type Ca2+channels, were most effective inhibitor of the 5-HT-induced contractions. While Sr2+ and Co2+ at a concentration of 100μM did not have a significant effect. The order effectiveness of inhibition was Cd2+ >>Mn2+>Mg2+=Ni2+=Zn2+. Bay K 8644 (1μM), a L-type Ca2+channel activator, did not influence the contractile response of the longitudinal muscle strip to 5-HT (3μM). The present results suggest that 5-HT may mainly act on N-type Ca2+channels in the myenteric neurones and cause the release of at least acetylcholine and substance P to induce contractions of the longitudinal muscle in the guinea-pig distal colon.
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