Contractile responses of longitudinal muscle strip to 5-HT and influences of divalent cations in the guinea-pig isolated colon.

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 (10 nM-10 microM) produced phasic contractions which were partially inhibited by atropine (1 microM) and markedly inhibited by tetrodotoxin (1 microM), 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 (3 microM) was almost completely inhibited by spantide (10 microM), a substance P antagonist, in the presence of atropine (1 microM), 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 (10 mu-100 microM), 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 100 microM did not have a significant effect. The order effectiveness of inhibition was Cd2+ >> Mn2+ > Mg2+ = Ni2+ = Zn2+. Bay K 8644 (1 microM), a L-type Ca2+ channel activator, did not influence the contractile response of the longitudinal muscle strip to 5-HT (3 microM). 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.