Cyclic AMP-mediated regulation of excitation-contraction coupling in canine gastric smooth muscle.

摘要: 1. Agonists known to increase cyclic AMP levels in gastrointestinal smooth muscles were studied isolated circular of the canine antrum investigate mechanisms inhibitory effects these agents. 2. Muscles electrically active, generating typical slow wave activity. Cytosolic Ca2+ ([Ca2+]cyt; measured by Indo-1 fluorescence) and tension increased response waves. 3. Stimulation isoprenaline (via beta 2-receptors) or forskolin, presence absence acetylcholine, inhibited plateau phase reduced phasic [Ca2+]cyt contractile responses. 4. Vasoactive intestinal peptide (VIP) calcitonin gene-related (CGRP), had similar forskolin. 5. Increases waves associated increases caused direct activation voltage-dependent channels Bay K 8644 (0.1 microM) also 6. Isoprenaline forskolin induced negative chronotropic effects, but VIP frequency. 7. At a given level [Ca2+]cyt, contractions greater under control conditions than isoprenaline, CGRP, suggesting that part inhibition produced agents may be due decreased sensitivity apparatus. 8. Experiments performed on alpha-toxin-permeabilized confirmed AMP-dependent involve Addition (3-300 reduction Ca(2+)-induced contraction at constant (pCa 5.5). 9. These results suggest probably subsequent protein kinase A: (i) decrease an influx during waves, (ii) apparatus [Ca2+]cyt. The membrane might occur directly indirectly increasing open probability K+ which would tend cause premature repolarization