ACTIVATION OF OPIOID AND MUSCARINIC RECEPTORS STIMULATES BASAL ADENYLYL-CYCLASE BUT INHIBITS CA2+ CALMODULIN-STIMULATED AND FORSKOLIN-STIMULATED ENZYME-ACTIVITIES IN RAT OLFACTORY-BULB/

In rat olfactory bulb, muscarinic and opioid receptor agonists stimula te basal adenylyl cyclase activity in a GTP-dependent and pertussis to xin-sensitive manner. However, in the present study, we show that in t he same brain area activation of these receptors causes inhibition of adenylyl cyclase activity stimulated by Ca2+ and calmodulin (CaM) and by forskolin (FSK), two direct activators of the catalytic unit of the enzyme. The opioid and muscarinic inhibitions consist of a decrease o f the maximal stimulation elicited by either CaM or FSK, without a cha nge in the potency of these agents. [Leu(5)]Enkephalin and selective d elta- and mu-, but not kappa-, opioid receptor agonists inhibit the FS K stimulation of adenylyl cyclase activity with the same potencies dis played in stimulating basal enzyme activity. Similarly, the muscarinic inhibition of FSK-stimulated adenylyl cyclase activity shows agonist and antagonist sensitivities similar to those characterizing the musca rinic stimulation of basal enzyme activity. Fluoride stimulation of ad enylyl cyclase is not affected by either carbachol or [Leu(5)]enkephal in. In vivo treatment of olfactory bulb with pertussis toxin prevents both opioid and muscarinic inhibition of Ca2+/ CaM- and FSK-stimulated enzyme activities. These results indicate that in rat olfactory bulb delta- and mu-opioid receptors and muscarinic receptors, likely of the M4 subtype, can exert a dual effect on cyclic AMP formation by intera cting with pertussis toxin-sensitive GTP-binding protein(s) and possib ly by affecting different molecular forms of adenylyl cyclase.