Postjunctional alpha 1- and beta-adrenoceptor effects of noradrenaline on electrical slow waves and phasic contractions of cat colon circular muscle.
1. The postjunctional excitatory and inhibitory effects of noradrenaline and selective alpha 1- and beta-adrenoceptor agonists on electrical and mechanical activity of cat colon muscle strips were studied by microelectrode recordings and isometric force measurements. Experiments were performed in the presence of tetrodotoxin (0.5 microM) or atropine (0.5 microM). 2. Circular muscle cells near the submucosal border had a mean resting membrane potential of -76.1 +/- 1.2 mV and exhibited electrical slow waves at frequencies of 4-6 cycles min-1. The mean values of electrical slow wave components were: upstroke potential, -40.7 +/- 1.2 mV; plateau potential, -43.7 +/- 0.8 mV; and duration, 4.9 +/- 0.4 s. Electrical slow waves were in phase with rhythmic contractions of the circular muscle layer. Muscle cells near the myenteric border had a mean testing membrane potential of -51.1 +/- 5.5 mV and did not exhibit electrical slow waves. 3. Noradrenaline (1 microM) increased the duration of electrical slow waves. This effect was inhibited by prazosin (1 microM) and potentiated by propranolol (5 microM), indicating activation of alpha 1- and beta-adrenoceptors. Also, when alpha 1-adrenoceptors were irreversibly blocked by phenoxybenzamine (1 microM), noradrenaline decreased the duration of electrical slow waves. Phenylephrine (1 microM), a selective alpha 1-adrenoceptor agonist, and isoprenaline (1 microM), a beta-adrenoceptor agonist, increased or decreased the duration of electrical slow waves, respectively. 4. Phenylephrine (0.01-5 microM) caused a linear increase in the area of electrical slow waves and phasic contractions but did not affect resting membrane potential or resting muscle tension. Higher concentrations of phenylephrine (5-50 microM) depolarized the resting membrane potential (2-6 mV) and increased muscle tone. 5. Nitrendipine or verapamil (each at 5 microM) reduced the amplitude of the upstroke potential and nearly abolished the plateau phase of the electrical slow waves. In the presence of L-type Ca2+ antagonists, noradrenaline (1-10 microM) or phenylephrine (1-100 microM) had no effect on electrical slow waves and phasic contractions. This indicates that the effects of noradrenaline and phenylephrine involve the influx of extracellular Ca2+ through voltage-dependent L-type Ca2+ channels. 6. Ryanodine, an alkaloid that depletes intracellular Ca2+ stores nearly abolished phasic contractions. In muscle strips, pretreated with ryanodine (10 microM for 30 min), phenylephrine (1 microM) increased and isoprenaline (1 microM) decreased the duration of electrical slow waves but neither was able to reverse the ryanodine-suppressed phasic contractions. This suggests that adrenoceptor effects on electrical slow waves are coupled to contractions via Ca2+ release from ryanodine-sensitive intracellular stores. 7. In summary, noradrenaline activates postjunctional alpha 1- and beta-adrenoceptors. Activation of alpha 1-adrenoceptors increases the magnitude of electrical slow waves and phasic contractions, whereas activation of beta-adrenoceptors decreases them. The alpha 1-adrenoceptor mediated effects on electrical slow waves and phasic contractions require the influx of Ca2+ through voltage-gated L-type Ca2+ channels. Phasic contractions also involve Ca2+ release from ryanodine-sensitive intracellular stores.
Venkova
K
K
Department of Physiology, Michigan State University, East Lansing, USA.
Krier
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002415:Cats; D003106:Colon / Q000187:drug effects*; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010528:Peristalsis / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D012433:Ryanodine; D010656:Phenylephrine; D009568:Nitrendipine; D014700:Verapamil; D007545:Isoproterenol; D009638:Norepinephrine