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Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A 1 and A 2A subtype receptor agonists
Author(s) -
Schindler Charles W,
KarczKubicha Marzena,
Thorndike Eric B,
Müller Christa E,
Tella Srihari R,
Ferré Sergi,
Goldberg Steven R
Publication year - 2005
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.0706043
Subject(s) - cgs 21680 , adenosine , agonist , adenosine a1 receptor , medicine , endocrinology , adenosine receptor , adenosine receptor antagonist , antagonist , chemistry , caffeine , pharmacology , receptor antagonist , receptor
1 The cardiovascular effects of the adenosine A 1 receptor agonist N 6 ‐cyclopentyladenosine (CPA) and the adenosine A 2A receptor agonist 2‐ p ‐(2‐carboxyethyl)phenethylamino‐5′‐ N ‐ethylcarboxamidoadenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate. 2 Intraperitoneal (i.p.) injections of the adenosine A 1 receptor agonist CPA led to dose‐dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg −1 CPA were antagonized by i.p. injections of the adenosine A 1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethyl‐xanthine (CPT), but not by i.p. injections of the adenosine A 2A receptor antagonist 3‐(3‐hydroxypropyl)‐8‐( m ‐methoxystyryl)‐7‐methyl‐1‐propargylxanthine phosphate disodium salt (MSX‐3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8‐sulfophenyltheophylline (8‐SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardiovascular effects of CPA. 3 The adenosine A 2A agonist CGS 21680 given i.p. produced a dose‐dependent decrease in blood pressure and an increase in heart rate. These effects of 0.5 mg kg −1 CGS 21680 were antagonized by i.p. injections of the adenosine A 2A receptor antagonist MSX‐3, but not by i.p. injections of the antagonists CPT, 8‐SPT or caffeine. 4 Central administration (intracerebral ventricular) of CGS 21680 produced an increase in heart rate, but no change in blood pressure. MSX‐3 given i.p. antagonized the effects of the central injection of CGS 21680. 5 These results suggest that adenosine A 1 receptor agonists produce decreases in blood pressure and heart rate that are mediated by A 1 receptors in the periphery, with little or no contribution of central adenosine A 1 receptors to those effects. 6 The heart rate increasing effect of adenosine A 2A agonists appears to be mediated by adenosine A 2A receptors in the central nervous system. The blood pressure decreasing effect of adenosine A 2A agonists is most probably mediated in the periphery.British Journal of Pharmacology (2005) 144 , 642–650. doi: 10.1038/sj.bjp.0706043