Spontaneous activity and its cholinergic modulation in circular smooth muscle isolated from guinea-pig stomach antrum.
Circular smooth muscle isolated from the guinea-pig gastric antrum generated periodic slow potentials in the presence of nifedipine and nitroarginine to prevent the activity of voltage-gated L-type Ca-channels and endogenous production of NO respectively. Chelerythrine, an inhibitor of protein kinase C (PKC), in the concentration range 10(-7)-3 x 10(-7) M reduced the frequency but not the amplitude of spontaneous slow potentials without altering the resting membrane potential. 2-Aminoethoxydiphenyl borate (2-APB, 3 x 10(-6) M), an inhibitor at inositol-1,4,5-trisphosphate (IP(3)) receptors, depolarized the membrane, increased the frequency and reduced the amplitude of the slow potentials; the latter actions were independent of depolarization. Two different phorbol esters, phorbol 12,13-dibutyrate and phorbol-12-myristate-13-acetate, increased the frequency of slow potentials, without altering the amplitude or changing the resting membrane potential; the effects of phorbol esters were antagonized by chelerythrine. Stimulation of muscarinic receptors with acetylcholine (ACh), in concentrations below those causing membrane depolarization (3 x 10(-8)-10(-7) M), increased the amplitude and frequency of slow potentials. Chelerythrine inhibited the ACh-induced increase in the frequency of slow potentials but did not prevent the increase in their amplitude. 2-APB inhibited the ACh-induced increase in the amplitude of slow potentials but did not prevent the increase in their frequency. These results suggest that the frequency of spontaneous slow potentials is regulated by PKC and their amplitude by IP(3) production. ACh increases both the amplitude and frequency of slow potentials; the former is related to the activation of PKC, while the latter is related to activation of IP(3)-receptors.
Department of Physiology, Nagoya City University Medical School, Mizuho-ku, 467-8601 Nagoya, Japan. eririn@med.nagoya-cu.ac.jp
Eri
E
Nakamura
Hikaru
H
Suzuki
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001896:Boron Compounds / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005746:Gastric Emptying / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D010617:Phenanthridines / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011706:Pyloric Antrum / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D000470:Alkaloids; D053119:Benzophenanthridines; D001896:Boron Compounds; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010617:Phenanthridines; D010703:Phorbol Esters; D018160:Receptors, Cytoplasmic and Nuclear; C016299:chelerythrine; C109986:2-aminoethoxydiphenyl borate; D011493:Protein Kinase C; D000109:Acetylcholine