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 si gnal detection system, which can integrate signals arising via G(s)- a nd Ca2+-mediated pathways. The occurrence of this adenylyl cyclase in brain regions implicated with associative learning in invertebrates an d with the mammalian model of plasticity - hippocampal long-term poten tiation, supports the notion that the ability of this species of adeny lyl cyclase to detect two signals simultaneously may pray a role in th is neuronal function. In the present study, two recently cloned, close ly-related adenylyl cyclases (Types V and VI), are shown to be inhibit ed by physiological elevation in [Ca2+](i). As a first step towards pr obing 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 f ound, ranging from a highly selective distribution of Type V mRNA with in the striatum, nucleus accumbens and olfactory tubercle, to a weak a nd ubiquitous distribution of Type VI mRNA. Type V AC mRNA is expresse d exclusively in medium-sized striatal neurons, which also express D-1 -dopaminergic (G(s)-linked) and M(1)-muscarinic cholinergic (Ca2+-link ed) receptors. Thus the adenylyl cyclase is primed for simultaneous de tection of opposing regulatory influences. The utility of this novel m ode of signal detection to dopaminergic function remains to be establi shed.