Opiate and dopamine stimulate different GTPase in striatum: evidence for distinct modulatory mechanisms of adenylate cyclase.
Previous studies demonstrated that opiate inhibition of adenylate cyclase (AC) in striatal membranes is related to an opiate-stimulated GTPase with a low Km. Dopamine (DA) also dose-dependently activates a high affinity GTPase, with a pattern of stimulation and a receptor selectivity (D1 type) similar to those observed in DA activation of striatal AC. Moreover, the DA- and the opiate-sensitive GTPase activities have different sensitivities to agents that affect the inhibition of AC, such as Na+ and N-ethylmaleimide (NEM), or the stimulation, such as cholera toxin (CTX). Thus, the impairment of opiate-dependent inhibition of AC in the absence of Na+ ions or after NEM pretreatment of the membranes is parallel with preferential impairment of the opiate-dependent GTPase. On the contrary, selective blocking by CTX of the DA-dependent GTPase leads to the enhancement of AC stimulation by DA. These results suggest that DA activation of striatal AC is related to a GTPase that is specifically stimulated by DA and is associated with the Ns protein. A distinct Ni protein seems to be responsible for the opiate effect on AC and GTPase.
Tirone
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Parenti
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Groppetti
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005033:Ethylmaleimide / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013237:Stereoisomerism
D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D002772:Cholera Toxin; D012964:Sodium; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D000262:Adenylyl Cyclases; D005033:Ethylmaleimide; D004298:Dopamine