REGULATION OF ADENYLYL-CYCLASE ISOFORMS BY N-ALKANOLS

We examined the effect of n-alkanols on adenylyl cyclase isoforms (typ es II and V) overexpressed in insect cells. Ethanol stimulated the typ e II isoform but not the type V isoform. Ethanol stimulated type II ad enylyl cyclase greater than GTP gamma S, and the treatment of the memb rane with GDP beta S or cholera toxin did not affect this stimulation. Other n-alkanols inhibited type V adenylyl cyclase activity in propor tion to their lipophilic potency. In contrast, type II adenylyl cyclas e was stimulated by weakly lipophilic n-alkanols and inhibited by stro ngly lipophilic n-alkanols. When solubilized membranes and purified pr eparations were used, all the n-alkanols inhibited type II adenylyl cy clase. Our data suggest that n-alkanols regulated adenylyl cyclase iso form-dependently. Stimulation of the type II isoform was independent f rom the interaction with Gs alpha but required the presence of an inta ct membrane structure. Our study may provide another step to understan ding how membrane protein subtypes are differentially regulated by n-a lkanols. (C) 1997 Wiley-Liss, Inc.