BaCl2-induced contractions in the guinea pig ileum longitudinal muscle: role of presynaptic release of neurotransmitters and Ca2+ translocation in the postsynaptic membrane.
Early studies indicated that the baCl2-induced contractions in the guinea pig ileum longitudinal muscle strip (GPI-LMS) were, in part, neuronal in origin. However, recent studies have suggested that BaCl2-induced contractions were produced by an action directly on the smooth muscle membrane. The purpose of this study was to investigate the mechanism of the BaCl2 contractions in the GPI-LMS. Botulinum toxin (5 x 10(5) MLD/mL), which blocks the electrically induced release of acetylcholine (ACh), hemicholinium-3 (HC-3; 110 micro M), which blocks ACh synthesis, tetrodotoxin (TTX; 60 nM), which blocks Na+ channels, black widow spider venom, which depletes the presynaptic neuron of neurotransmitter, and atropine (2.9 micro M), a potent muscarinic antagonist, had no effect on the BaCl2 contractions. Densensitization of the GPI-LMS to substance P did not affect the BaCl2 contraction. In Ca2+ -free buffer the BaCl2 dose-response curve was shifted to the right. In Ca2+-free solution the time to 50% inhibiton of the contractile response to ACh (73 nM) and BaCl2 (1.16 mM) was 3.7 and 125 min, respectively. The D 600 Ic50 for ACh and BaCl2 contractions was 220 and 130 nM, respectively. In Ca2+-free buffer either EGTA (0.53 mM) or D 600 (1 micro M) were potent inhibitors of BaCl2 contractions. These results suggest that in the GPI-LMS the BaCl2 response is not mediated by a release of ACh (or substance P) because inhibitors of ACh release, synthesis, and receptors do not affect the responses. Also, the BaCl2 contraction is not due to activation of Na+ channels because TTX is without effect. The BaCl2-induced contraction appears to be mainly due to the movement of membrane bound Ca2+ through D 600 sensitive Ca2+ channels with extracellular Ca2+ and possible passage of Ba2+ ions intracellularly playing relatively minor roles.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001464:Barium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D001905:Botulinum Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006426:Hemicholinium 3 / Q000494:pharmacology; D007082:Ileum / Q000502:physiology*; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D013111:Spider Venoms; D001464:Barium; D006426:Hemicholinium 3; D013779:Tetrodotoxin; D001285:Atropine; D001905:Botulinum Toxins; D002118:Calcium