Adenosine Regulates the Ca2+ Sensitivity of Mast Cell Mediator Release

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1988 Dec 1

PMID 2461558

Citations 4

Authors

M J Lohse

K N Klotz

M J Salzer

U Schwabe

Affiliations

Soon will be listed here.

Abstract

Mast cells release histamine and other mediators of allergy in response to stimulation of their IgE receptors. This release is generally thought to be mediated by an elevation of cytosolic Ca2+. Recent evidence suggests that there might be factors that modulate the coupling between Ca2+ levels and mediator release. The present report identifies adenosine as one such modulator. Adenosine and several of its metabolically stable analogues were shown to enhance histamine release from rat peritoneal mast cells in response to stimuli such as concanavalin A. Metabolizing endogenous adenosine with adenosine deaminase dampened the response to stimuli, whereas trapping endogenous adenosine inside mast cells with nucleoside-transport inhibitors markedly enhanced stimulated histamine release. The metabolically stable adenosine analogue 5'-(N-ethylcarboxamido)adenosine (NECA) did not affect the initial steps in the sequence from IgE-receptor activation to mediator release, which are generation of inositol trisphosphate and increase of cytosolic Ca2+. However, NECA did enhance the release induced in ATP-permeabilized cells by exogenous Ca2+, but it had no effect on the release induced by phorbol esters. These data suggest that adenosine sensitizes mediator release by a mechanism regulating stimulus-secretion coupling at a step distal to receptor activation and second-messenger generation.

Citing Articles

Mast cell adenosine induced calcium mobilization via Gi3 and Gq proteins.

Hoffman H, Walker L, Marquardt D Inflammation. 1997; 21(1):55-68.

PMID: 9179622 DOI: 10.1023/a:1027390825353.

A1 adenosine receptors expressed in CHO-cells couple to adenylyl cyclase and to phospholipase C.

Freund S, Ungerer M, Lohse M Naunyn Schmiedebergs Arch Pharmacol. 1994; 350(1):49-56.

PMID: 7935854 DOI: 10.1007/BF00180010.

Inhibition of protein kinase A fails to alter mast cell adenosine responsiveness.

Marquardt D, Walker L Agents Actions. 1994; 43(1-2):7-12.

PMID: 7741046 DOI: 10.1007/BF02005755.

Synergistic effects of calcium-mobilizing agents and adenosine on histamine release from rat peritoneal mast cells.

Lohse M, Maurer K, Klotz K, Schwabe U Br J Pharmacol. 1989; 98(4):1392-8.

PMID: 2482106 PMC: 1854830. DOI: 10.1111/j.1476-5381.1989.tb12689.x.

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