Adenylate Cyclase Modulation by Ammonium Ion: GTP-like Effect on Muscarinic and α2-Adrenergic Receptors

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Abstract
The stimulatory influence of ammonium sulfate on adenylate cyclase activity was investigated. By competition binding experiments on the .beta.-adrenergic stimulatory receptor in rat myocardial membranes, no influence could be detected of ammonium sulfate either in receptor coupling to the stimulatory guanine nucleotide binding protein or in the GTP-induced uncoupling. In order to detect an impaired inhibition instead of an increased stimulation of adenylate cyclase activity by ammonium sulfate the investigation was extended to inhibitory receptors. The same type of effect by ammonium sulfate was detected on both the muscarinic cholinergic receptor in rat myocardial membranes as well as on the .alpha.2-adrenergic receptor in human platelets. The influence of ammonium sulfate noted in competition binding studies and off-kinetics experiments was GTP-like, i.e., causing a decrease in agonist-receptor affinity leaving all the inhibitory receptors in the low affinity state. The observed stimulatory effect of ammonium sulfate is exerted by the ammonium ion on the inhibitory guanine nucleotide binding protein, impairing the negative control of adenylate cyclase activity.