Role of nitric oxide/cyclic GMP in myocardial adenosine A1 receptor-inotropic response.

Abstract:

:In this study we have determined the different signalling pathways involved in adenosine A(1)-receptor (A(1)-receptor)-dependent inhibition of contractility in rat isolated atria. N-cyclopentyladenosine (CPA) stimulation of A(1)-receptor exerts: negative inotropic response, inositol phosphates accumulation, stimulation of nitric oxide synthase (NOS), increased production of nitric oxide (NO) and cyclic GMP. Inhibitors of phospholipase C (PLC), protein kinase C (PKC), calcium/calmodulin, NOS and guanylate cyclase shifted the dose-response curve of CPA on contractility to the right. Those inhibitors also attenuated the A(1)-receptor-dependent increase in cyclic GMP and activation of NOS. These results suggest that CPA activation of A(1)-receptors exerts a negative inotropic effect associated with increased production of nitric oxide and cyclic GMP. The mechanism appears to occur secondarily to stimulation of phosphoinositide turnover via PLC activation. This, in turn, triggers cascade reactions involving calcium/calmodulin and PKC, leading to activation of NOS and soluble guanylate cyclase.

journal_name

Br J Pharmacol

authors

Sterin-Borda L,Gómez RM,Borda E

doi

10.1038/sj.bjp.0704487

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

444-50

issue

2

eissn

0007-1188

issn

1476-5381

journal_volume

135

pub_type

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