A Central Role for Magnesium in the Regulation of Inhibitory Adenosine Receptors
Many adenylate cyclase systems are being recognized to be subject to both stimulation and inhibition of activity, which is mediated by distinct sets of receptors (1,2). Evidence is accumulating that distinct GTP regulatory proteins are associated with both classes of receptor, although it is not clear whether the GTP regulatory proteins are discrete or part of a large complex. The GTP regulatory proteins serve two major functions: firstly, they transmit the signal of receptor occupancy into either an increase or a decrease in catalytic activity; secondly, they regulate binding of effectors to their receptors (3). The ability to measure these two functions separately uncovers anomalies in our understanding of the communication between receptor, GTP regulatory protein and catalytic unit. Discrepancies are generally encountered between the properties of receptors when judged from the regulation of cyclase activity, compared with their properties as judged by guanine nucleotide regulation of receptor binding. This is particularly apparent in the case of receptors which mediate inhibition of adenylate cyclase. The non-hydrolyzable guanine nucleotide analogues are as effective as GTP at regulating receptor binding; these analogues also promote a characteristic transient inhibition of activity, although they are ineffective in the promotion of receptor-mediated inhibition of activity (1,2).
KeywordsAdenylate Cyclase Adenosine Receptor Guanine Nucleotide Scatchard Analysis Sodium Cholate
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