Degranulation of rat omental mast cells by A(1) receptor agonists in vitro

The haemodynamic effects of adenosine are thought to result in part from a release of mast cell amines via A3 receptor stimulation. To investigate the nature of the receptors involved in adenosine-induced mast cell degranulation in the rat isolated omentum we have used adenosine analogues with varying specificities as activators of the A(1), A(2) and A(3) receptors, and antagonists with differing specificities for A(1) and A(2) receptors. Analogues which act predominantly as A(1) (e.g. N(6)-cyclopentyladenosine) or as mixed A(1)/A(2) receptor agonists (e.g. adenosine, inosine, 5'-(Nethylcarboxamido) adenosine) caused mast cell degranulation, whereas a predominantly A3 receptor agonist (IB-MECA) was inactive. Pre-treatment of the omentum with the A(1)/A(2) receptor antagonist 8-phenyltheophylline or with the more specific A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine significantly reduced agonist-induced degranulation. Pre-treatment with disodium cromoglycate or with BN52021 also reduced degranulation of mast cells in response to N(6)-cyclopentyladenosine. In the rat isolated omental mast cell we conclude that degranulation is an indirect result of A(1) receptor stimulation. Platelet-activating factor release appears to mediate at least part of the degranulation.