Adenylyl cyclase types I and VI but not II and V are selectively inhibited by nitric oxide

GOLDSTEIN J, SILBERSTEIN C, IBARRA C

BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH

ssociacao Brasileira De Divulgacao Cientifica

Año: 2002 vol. 35 p. 145 - 151

0100-879X

Adenylyl cyclase (AC) isoforms catalyze the synthesis of 3´,5´-cyclicAMP from ATP. These isoforms are critically involved in the regulationof gene transcription, metabolism, and ion channel activity amongothers. Nitric oxide (NO) is a gaseous product whose synthesis from Larginineis catalyzed by the enzyme NO synthase. It has been wellestablished that NO activates the enzyme guanylyl cyclase, but littlehas been reported on the effects of NO on other important secondmessengers, such as AC. In the present study, the effects of sodiumnitroprusside (SNP), a nitric oxide-releasing compound, on COS-7cells transfected with plasmids containing AC types I, II, V and VIwere evaluated. Total inhibition (~98.5%) of cAMP production wasobserved in COS-7 cells transfected with the AC I isoform andpreviously treated with SNP (10 mM) for 30 min, when stimulatedwith ionomycin. A high inhibition (~76%) of cAMP production wasalso observed in COS-7 cells transfected with the AC VI isoform andpreviously treated with SNP (10 mM) for 30 min, when stimulatedwith forskolin. No effect on cAMP production was observed in cellstransfected with AC isoforms II and V.