BETA-ADRENERGIC INHIBITION OF ELECTRICAL AND MECHANICAL-ACTIVITY IN CANINE COLON - ROLE OF CAMP

The effects of beta-adrenergic receptor stimulation on the electrical and mechanical activity of canine colonic circular muscles were compar ed with forskolin (Fsk), a known stimulator of adenylate cyclase. The actions of isoproterenol (Iso) were mediated by beta2-receptors. Iso a nd Fsk increased intracellular adenosine 3',5'-cyclic monophosphate (c AMP) levels in both the presence and absence of acetylcholine (ACh), w hereas ACh (0.3 muM) alone reduced cAMP levels. These agents caused in hibition of spontaneous and ACh-induced contractions. Inhibition was a ssociated with a reduction in the amplitude and duration of electrical slow waves recorded near the submucosal border. Near the myenteric bo rder, Iso and Fsk hyperpolarized the membrane by up to 30 mV and chang ed the pattern of electrical rhythmicity. These effects were mimicked by 8-bromo-cAMP (1-3 mM). Contractile inhibition with Fsk and Iso was associated with a decrease in the amplitude and duration of Ca2+ trans ients measured with fura-2 fluorescence. cAMP (10-300 muM) reduced the Ca2+ sensitivity of the contractile apparatus in muscles permeabilize d with staphylococcal a-toxin. The actions of Iso appear linked to cAM P. We hypothesize that cAMP produces relaxation both by modulation of membrane ionic channels with a consequent decline in the entry of Ca2 as well as through a decrease in the sensitivity of the contractile a pparatus to Ca2+.