Excitation of smooth muscles isolated from the guinea-pig gastric antrum in response to depolarization.
In small segments of circular smooth muscle bundle isolated from the guinea-pig gastric antrum, depolarization of the tissue with intracellular current stimuli evoked regenerative slow potentials after a refractory period of 5-10 s. The refractory period changed inversely with the amplitude and duration of the stimulating depolarization. Thapsigargin (an inhibitor of calcium-ATPase at internal stores), 2-aminoethoxydiphenyl borate (2-APB, an inhibitor of inositol 1,4,5-trisphosphate (IP3)-receptor-mediated Ca2+ release), and carbonyl cyanide m-chlorophenyl-hydrazone (a mitochondrial protonophore) reduced the amplitude of slow potentials, with no significant alteration of the refractory period. Bisindolylmaleimide I or chelerythrine (inhibitors of protein kinase C, PKC) increased the refractory period and inhibited the amplitude of slow potentials. These results indicate that the refractory period and amplitude of slow potentials are related to the activation of PKC and the amount of Ca2+ released from the internal stores through activation of IP3 receptors, respectively. Acetylcholine (ACh) reduced the refractory period and increased the amplitude of slow potentials: the former was antagonized by chelerythrine and the latter by 2-APB. The results suggest that ACh has dual actions; stimulation of the metabolism of inositol phosphate and activation of PKC. Phorbol-12-myristate-13-acetate, a selective stimulant of PKC, at low concentrations (< 10 nM) mimicked the actions of ACh and at high concentrations reduced the frequency of slow potentials and increased the refractory period. The possible involvement of the concentration-dependent differences in the actions of phorbol ester on the translocation of PKC was considered.
Kito
Yoshihiko
Y
Department of Physiology, Nagoya City University Medical School, Mizuho-Ku, Nagoya 467-8601, Japan.
Fukuta
Hiroyasu
H
Yamamoto
Yoshimichi
Y
Suzuki
Hikaru
H
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009130:Muscle, Smooth / Q000502:physiology*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011706:Pyloric Antrum / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D001896:Boron Compounds; D002273:Carcinogens; D004791:Enzyme Inhibitors; D007211:Indoles; D007476:Ionophores; D008301:Maleimides; D010617:Phenanthridines; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D019284:Thapsigargin; D007811:Lanthanum; C016299:chelerythrine; C109986:2-aminoethoxydiphenyl borate; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium