CAMP-mediated regulation of chloride secretion by the opercular epithelium.

Abstract

Catecholamine regulation of the Cl- secretion rate (short-circuit current, Isc) and adenosine 3',5'-cyclic monophosphate (cAMP) levels of the opercular epithelium was investigated by using 3-isobutyl-1-methylxanthine (IBMX), forskolin, and adrenergic agonists. In this tissue alpha-adrenergic agonists inhibit, and beta-adrenergic agonists stimulate, the Isc (J. Physiol. London 294: 483-495, 1979). IBMX and forskolin stimulated the Isc 125 and 85%, respectively, and simultaneously produced 2.5- and 70.0-fold elevations in the cAMP levels, respectively. These findings confirm previous observations demonstrating that stimulation of the Isc in this tissue is mediated by elevations in cAMP (J. Comp. Physiol. B 145: 29-35, 1981). Isoproterenol, a beta-agonist, had no effect on the Isc of either IBMX- or forskolin-stimulated tissues but increased the cAMP level an additional 5.8-fold in IBMX-stimulated tissues. Clonidine, an alpha-agonist, inhibited the Isc in IBMX-stimulated tissues only and had no effect on cAMP levels in either IBMX- or forskolin-stimulated tissues. These findings demonstrate that catecholamine-induced inhibition of the Isc can occur while the cAMP level remains elevated, indicating that this effect is not mediated by lowering cAMP levels. This observation is strong evidence for a cAMP-independent mechanism for catecholamine-induced inhibition of Cl- secretion in the opercular and similar epithelia.