MAST-CELL DEGRANULATION FOLLOWING ADENOSINE A(3) RECEPTOR ACTIVATION IN RATS

The present studies were carried out to provide further evidence for t he hypothesis that the hypotensive response to adenosine A(3) receptor activation in the anaesthetized rat involves mediator release from ma st cells. Male Sprague-Dawley rats were anaesthetized and given just s upramaximal hypotensive doses of either the non-selective A(3) recepto r agonist, N-6-2-(4-aminophenyl)ethyladenosine (APNEA: 100 mu g/kg, pr eceded by the A(1)/A(2) receptor antagonist, 8-p-(sulphophenyl)theophy lline, to 'isolate' the A(3) receptor-mediated component of the respon se), the mast cell degranulating agent, compound 48/80 (300 mu g/kg) o r the vehicle for APNEA, intravenously. Blood was withdrawn from a car otid artery between 2 and 10 min after the injection and plasma and se rum histamine concentrations measured. Samples of connective tissue (s urrounding the abdominal musculature), thymus, mesenteric lymph node, kidney, skin and diaphragm were removed for histological analysis. The plasma and serum histamine concentrations were markedly and significa ntly higher in the APNEA- or compound 48/80-treated animals compared t o vehicle-treated controls. Consistent with this, a substantially grea ter proportion of mast cells was seen to be undergoing degranulation i n all tissues removed from animals treated with APNEA or compound 48/8 0 compared to those from rats treated with vehicle. Thus, adenosine A( 3) receptor activation results in rapid mast cell degranulation in the anaesthetized rat. The data provide further evidence of a key role fo r the mast cell in adenosine A(3) receptor-mediated hypotension in thi s species.