Nitric oxide regulates adenylyl cyclase activity in rat striatal membranes.
The regulation of adenylyl cyclase activity by nitric oxide (NO) was studied in rat (Sprague-Dawley) striatal membranes. Three chemically distinct NO donors attenuated forskolin-stimulated activity but did not alter basal activity. Maximum inhibition resulted in a 50% decrease in forskolin-stimulated activity, consistent with the presence of multiple isoforms of adenylyl cyclase and our previous findings that only the forskolin-stimulated activity of the type-5 and -6 isoform family of enzymes is inhibited by NO. To monitor primarily the type-5 isoform, we examined the ability of NO donors to attenuate D(1)-agonist-stimulated adenylyl cyclase activity. Under those conditions, complete inhibition was observed. The data indicate that NO attenuates neuromodulator-stimulated cAMP signaling in the striatum.
Hudson
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Edward A. Doisy Department of Biochemistry and Molecular Biology, Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, Missouri 63104, USA.
Corbett
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Howlett
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Klein
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D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007536:Isomerism; D008566:Membranes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine
D020030:Nitric Oxide Donors; D009573:Nitrites; D009599:Nitroprusside; D005576:Colforsin; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D000262:Adenylyl Cyclases; D010396:Penicillamine