Calcium dependence of neurotensin stimulation of circular colonic muscle of the rabbit.
The effect of neurotensin on smooth muscle contraction was compared in strips from rabbit proximal and distal circular colonic muscle. The effective dose for neurotensin stimulation that caused a 50% response in both tissues was similar (1.3 X 10(-10) M). The maximal isometric stress, however, was greater in the distal colon than in the proximal colon (p less than 0.01). Neurotensin stimulation of both proximal and distal colon was unaffected by tetrodotoxin, phentolamine, propranolol, naloxone, or atropine. Neurotensin-stimulated contraction was inhibited by "Ca2+-free" (pCa = 5.1) or La3+ buffer. Verapamil (10(-6) M) or nitroprusside (10(-4) M) decreased neurotensin stimulation of proximal and distal colon by approximately 40% (p less than 0.05). Removal of Ca2+ from the buffer inhibited stimulation of muscle contraction by high extracellular potassium [( K+]o) more than bethanechol stimulation (p less than 0.01). La3+ (1 mM) inhibited the contraction stimulated by bethanechol or increased [K+]o. Although verapamil inhibited contraction by bethanechol and increased [K+]o by approximately 50%, nitroprusside had no effect on the contraction mediated by these stimulants. 8-Bromo-guanosine 3',5'-cyclic monophosphate (cGMP) inhibited neurotensin, but not [K+]o or bethanechol-stimulated contraction. These data suggest (a) neurotensin stimulated colonic contractions at a concentration that is potentially physiologic, (b) neurotensin stimulated colonic smooth muscle directly without neural mediation, (c) neurotensin stimulation of colonic muscle is controlled by [Ca2+]o and [cGMP]i.
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009496:Neurotensin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D001626:Bethanechol Compounds; D018723:Bethanechol; D009599:Nitroprusside; D009496:Neurotensin; D014700:Verapamil; D002118:Calcium