Synergistic effects of calcium-mobilizing agents and adenosine on
histamine release from rat peritoneal mast cells
Br J Pharmacol, 98 (4):
1392-8 (December 1989)Lohse, M J Maurer, K Klotz, K N Schwabe, U In Vitro England British
journal of pharmacology Br J Pharmacol. 1989 Dec;98(4):1392-8..Abstract
1. Adenosine and its metabolically stable analogue N-ethyl-carboxamidoadenosine
(NECA) enhance histamine release from rat peritoneal mast cells when
these are stimulated by calcium-mobilizing agents. NECA and adenosine
shift the concentration-response curve of the calcium ionophore A23187
to lower concentrations. 2. The potencies of NECA or adenosine in
enhancing A23187-induced histamine release are dependent on the level
of stimulated release in the absence of adenosine analogues. At high
levels of release their potencies are up to 20 times higher than
at low levels. Consequently, averaged concentration-response curves
of adenosine and NECA for enhancing histamine release are shallow.
3. The adenosine transport blocker S-(p-nitrobenzyl)-6-thioinosine
(NBTI) has no effect by itself at low levels of stimulated histamine
release, but abolishes the enhancing effect of adenosine. At high
levels of release, however, NBTI alone enhances the release of histamine.
4. It is concluded that adenosine and calcium reciprocally enhance
the sensitivity of the secretory processes to the effects of the
other agent. The levels of intracellular adenosine obtained by trapping
adenosine inside stimulated mast cells are sufficient to enhance
histamine release substantially, suggesting that this effect may
play a physiological and pathophysiological role.