SELECTIVE EXPRESSION OF ONE CA2+-INHIBITABLE ADENYLYL-CYCLASE IN DOPAMINERGICALLY INNERVATED RAT-BRAIN REGIONS

Type I adenylyl cyclase, which can be stimulated by elevated cellular levels of Ca2+, has been proposed to provide a positive coincidence signal detection system, which can integrate signals arising via G(s)- and Ca2+-mediated pathways. The occurrence of this adenylyl cyclase in brain regions implicated with associative learning in invertebrates and with the mammalian model of plasticity - hippocampal long-term potentiation, supports the notion that the ability of this species of adenylyl cyclase to detect two signals simultaneously may pray a role in this neuronal function. In the present study, two recently cloned, closely-related adenylyl cyclases (Types V and VI), are shown to be inhibited by physiological elevation in [Ca2+](i). As a first step towards probing the neuronal significance of Ca2+-inhibitable adenylyl cyclases, their distribution was evaluated by in situ hybridization analysis of the rat brain. Strikingly distinct patterns of gene expression were found, ranging from a highly selective distribution of Type V mRNA within the striatum, nucleus accumbens and olfactory tubercle, to a weak and ubiquitous distribution of Type VI mRNA. Type V AC mRNA is expressed exclusively in medium-sized striatal neurons, which also express D-1-dopaminergic (G(s)-linked) and M(1)-muscarinic cholinergic (Ca2+-linked) receptors. Thus the adenylyl cyclase is primed for simultaneous detection of opposing regulatory influences. The utility of this novel mode of signal detection to dopaminergic function remains to be established.