Selective expression of one Ca(2+)-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 Gs- and Ca(2+)-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 play 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 Ca(2+)-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 D1-dopaminergic (Gs-linked) and M1-muscarinic cholinergic (Ca(2+)-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.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
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D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000067956:Adenylyl Cyclase Inhibitors; D012333:RNA, Messenger; D002118:Calcium; D004298:Dopamine