Swelling of pig red cells leads to an increase in a chloride-dependent K flux which can be potentiated by CAMP, whereas cell shrinking causes a selective increase in Na movement which is mediated by a NaiH exchanger. We examined the influence of adenosine and adenosine receptor agonists on the volume-sensitive, ouabain-resistant, chloride-dependent K flux, referred to as Rb flux and volumeactivated Na/H exchange pathway. It was found that adenosine and adenosine receptor agonists inhibited the Rb flux. Nh-cyclohexyl adenosine (CHA) has been found to be the most potent inhibitor with EC,, of approximately 4.5 p,M followed by 2-chloroadenosine (CI-ado) with EC,, of approximately 27 pM and 5'-(N-ethyl)-carboxamido-adenosine (NECA) with EC,, of approximately 185 pM. CHA also inhibits the CAMP-stimulated Rbflux. However, CHA does not alter the basal intracellular cAMP level nor the intracellular cAMP content raised by exogenously added CAMP. In contrast to the adenosine agonist action on the Rb flux, Na/H exchange, which is activated upon cell shrinkage, exhibits a slight stimulation in response to CHA. These findings suggest that the presence of A , adenosine receptors on the surface of red cells influences the regulation of volume-activated ion transport.
Adenosine elicits diverse responses in a variety of cells, including an increase in blood flow (Berne, 19631, interference with synaptic transmission (Kuroda et al., 19761, inhibition of lipolysis (Trost and Stock, 1979), alteration of cAMP content (Gilman, 19841, and regulation of numerous ion channels. Physiological responses elicited by adenosine are presumably mediated by purinergic receptors, termed PI receptors, that are distinct from P2 type receptors for which ATP is the most potent agonist . As in most receptors, both PI and P2 receptors are further subdivided into subtypes. In the case of PI receptors, subtype receptors were initially distinguished depending on whether receptor activation leads to a stimulation or an inhibition of adenylyl cyclase activity. The former is termed R, or A2 and the latter is known as Ri or Al receptors