Different pathways for Ca2+ mobilization by angiotensin II and carbachol in the circular muscle of the guinea-pig ileum

Ca2+ pathways activated by angiotensin II and carbachol were evaluated in t he circular muscle of the guinea-pig ileum by recording mechanical and elec trical activities. Transient contractions induced by angiotensin II were gr eatly reduced by Ca2+ removal from the medium whereas carbachol-induced res ponses were not significantly altered. Nifedipine had no effect on the resp onses to both agonists. A high concentration of tetrodotoxin (0.1 mu M) inh ibited angiotensin II-induced contractile responses without affecting the d epolarization, whereas 1 mM Ni2+ inhibited the mechanical and electrical ef fects. Neither tetrodotoxin nor Ni2+ affected carbachol-induced effects. Th ese results indicate that angiotensin II-induced phasic contractions depend on extracellular Ca2+ but not on voltage-dependent L-type Ca2+ channels. I t is suggested that angiotensin II activates Ni2+-sensitive Na+ and non-spe cific cationic channels, whereas the responses to carbachol are dependent o n receptor-activated Ca2+ release. Furthermore the different response of th e longitudinal and circular muscles to the inhibitory effects of tetrodotox in and Ni2+ on the angiotensin II- and carbachol-induced contractions indic ates that these agonists exert their own myogenic effects on each layer and are able to trigger different Ca2+ mobilization pathways. (C) 1999 Elsevie r Science B.V. All rights reserved.