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.
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Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Cooper
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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