Adenosine A1 Receptors Mediate Mobilization of Calcium in Human Bronchial Smooth Muscle Cells

Adenosine stimulates contraction of airway smooth muscle, but the mechanism is widely considered indirect, depending on release of contractile agonists from mast cells and nerves. The goal was to determine whether adenosine, by itself, directly regulates calcium signaling in human bronchial smooth muscle cells (HBSMC). Primary cultures of HBSMC from normal subjects were loaded with fura 2-AM, and cytosolic calcium concentrations ([Ca2+]i) were determined ratiometrically by imaging single cells. The nonselective adenosine receptor agonist, 5′-N-ethylcarboxamidoadenosine (NECA), and the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA), both stimulated rapid, transient increases in [Ca2+]i. In contrast, there were no calcium responses to 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamido-adenosine (100 nM) or N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (100 nM), selective agonists at adenosine A2A receptors and adenosine A3 receptors, respectively. Calcium responses to NECA and CPA wer...