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Role of nitric oxide/cyclic GMP in myocardial adenosine A 1 receptor‐inotropic response
Author(s) -
SterinBorda Leonor,
Gómez Ricardo M,
Borda Enri
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704487
Subject(s) - nitric oxide , medicine , endocrinology , phospholipase c , calmodulin , chemistry , nitric oxide synthase , contractility , stimulation , adenosine , protein kinase c , receptor , calcium , signal transduction , biology , biochemistry
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.British Journal of Pharmacology (2002) 135 , 444–450; doi: 10.1038/sj.bjp.0704487