Specific potentiation by cyclic AMP of natriuretic peptide-mediated cyclic GMP production in adipose tissue.
Adipose tissue of the mesenteric territory contains large quantities of natriuretic peptide receptors (NPR) mainly of the NPR-C subtype. Guanylyl cyclase-bound receptors are also present since atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are equally potent in activating this enzyme. While searching for a potential biological role for NP in adipocytes we observed that ANP-mediated generation of cyclic GMP (cGMP) was potentiated when the cells were simultaneously treated with isoproterenol. Indeed, isoproterenol, a beta-adrenergic agonist, and forskolin, an activator of adenylyl cyclase, can both double or triple cGMP production in response to ANF stimulation. There was a direct correlation between the level of cyclic AMP (cAMP) generated and the level of NP-mediated cGMP production suggesting that a cAMP-dependent mechanism may be responsible of this potentiation. To determine whether or not this phenomenon was unique to adipocytes, NPR subtypes were characterized in 4 established cell lines and their cAMP-dependent cGMP behavior examined. A10 and A7r5 smooth muscle cells showed identical ratio of NPR subtypes with about 95% NPR-C and 5% NPR-B. PC12 cells presented 100% NPR-A and NIH 3T3 fibroblasts 50% NPR-C and 50% NPR-B. Regardless of the NPR subtype, forskolin could not potentiate the cGMP generation in these cell lines. These data indicate that the cAMP-dependent potentiation of the NP-mediated cGMP production is unique to adipocytes, appears independent of the guanylyl cyclase-linked NPR subtypes and may be involved in the sensitization of the guanylyl cyclase domain of NPR for a potential biological role of NP in the adipose tissue.
Thibault
G
G
Clinical Research Institute of Montreal, Québec, Canada. thibaug@IRCM.UMONTREAL.CA
Lacasse
A
A
Garcia
R
R
D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D020098:Natriuretic Peptide, C-Type; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D005576:Colforsin; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D007545:Isoproterenol