Jp. Hannon et al., A ROLE FOR MAST-CELLS IN ADENOSINE A(3) RECEPTOR-MEDIATED HYPOTENSIONIN THE RAT, British Journal of Pharmacology, 115(6), 1995, pp. 945-952
1 The adenosine A(3) receptor agonist, N-6-2-(4-aminophenyl)ethyladeno
sine (APNEA) induces hypotension in the anaesthetized rat. The present
experiments were carried out to explore the role of mast cells in the
response. 2 Intravenous injection of APNEA (1-30 mu g kg(-1) to rats
in which the A(3) receptor-mediated response had been isolated by pret
reatment with 8-(p-sulphophenyl) theophylline (8-SPT)), induced dose-r
elated falls in blood pressure accompanied at higher doses by small fa
lls in heart rate. Responses to the mast cell degranulating agent, com
pound 48/80 (10-300 mu g kg(-1), i.v.) were qualitatively similar to t
hose to APNEA. 3 Pretreatment with sodium cromoglycate (0.25-20 mg kg(
-1) i.v.) induced dose-related, although incomplete, blockade of the h
ypotensive responses to APNEA. At 20 mg kg(-1), sodium cromoglycate al
so inhibited the cardiovascular response to compound 48/80 but had no
effects on those to the selective A(1) receptor agonist, N-6-cyclopent
yladenosine (CPA) or the selective A(2A) receptor agonist, yethyl)phen
ylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680). Lodoxamide (0.01-
20 mg kg(-1)) also blocked selectively but incompletely the response t
o APNEA. 4 The cardiovascular responses to compound 48/80 (10-300 mu g
kg(-1), i.v.) were markedly suppressed in animals which had received
repeated doses of the compound by the intraperitoneal route. Similarly
APNEA was essentially devoid of cardiovascular activity in such prepa
rations. In contrast, responses to CPA were similar in animals treated
repeatedly with compound 48/80 to those obtained in control animals.
5 Plasma and serum histamine concentrations were markedly increased as
sociated with the pronounced hypotensive responses induced by intraven
ous injections of APNEA (30 or 100 mu g kg(-1)) in the presence of 8-S
PT, or compound 48/80 (300 mu g kg(-1)). 6 Taken together the data imp
licate the mast cell in a key role in adenosine A(3) receptor-mediated
hypotension in the anaesthetized rat.