ADENYLYL-CYCLASE MESSENGER-RNA EXPRESSION DOES NOT REFLECT THE PREDOMINANT CA2+ CALMODULIN-STIMULATED ACTIVITY IN THE HYPOTHALAMUS/

Only three (Types I, II, V) of the six currently-described subtypes of adenylyl cyclase are prominently expressed in the rat brain. These sp ecies are differently sensitive to Ca2+, beta gamma subunits of G-prot eins and protein kinase C. A knowledge of the susceptibility of the cA MP-signalling system in particular brain regions to these diverse mode s of regulation can shed light on the mechanism of action of the neuro transmitters that modify neuronal activity in such regions. Cyclic AMP is extensively involved in the physiological functions of the hypotha lamus. We have used in situ hybridization histochemistry with syntheti c oligonucleotides to examine the expression in the rat hypothalamus o f the three major brain subtypes of adenylyl cyclase-Ca2+/calmodulin-s timulable (Type I), Ca2+-insensitive (Type II) and Ca2+-inhibitable (T ype V). The hypothalamus expresses high levels only of Type II mRNA, p articularly in the supraoptic and paraventricular nuclei. Curiously, t he strong expression of the Ca2+-insensitive Type II mRNA and the lack of expression of the major brain specific Type I mRNA does not correl ate with the adenylyl cyclase activity, which is largely Ca2+/calmodul in stimulable in plasma membranes prepared from the hypothalamus.