Stimulation of Guanosine 5′‐O‐(3‐[35S]Thiotriphosphate) Binding by Cholinergic Muscarinic Receptors in Membranes of Rat Olfactory Bulb

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Abstract
In membranes of rat olfactory bulb, a brain region in which muscarinic agonists increase cyclic AMP formation, the muscarinic stimulation of guanosine 5′‐O‐(3‐[35S]thiotriphosphate) ([35S]GTPγS) binding was used as a tool to investigate the receptor interaction with the guanine nucleotide‐binding regulatory proteins (G proteins). The stimulation of the radioligand binding by carbachol (CCh) was optimal (threefold increase) in the presence of micromolar concentrations of GDP and 100 mM NaCl. Exposure to N‐ethylmaleimide and pertussis toxin markedly inhibited the CCh effect, whereas it increased the relative stimulation of [35S]GTPγS binding elicited by pituitary adenylate cyclase‐activating polypeptide (PACAP). On the other hand, membrane treatment with cholera toxin curtailed the PACAP stimulation of [35S]GTPγS binding but did not affect the response to CCh. Like CCh, a number of cholinergic agonists stimulated [35S]GTPγS binding in a concentration‐dependent and saturable manner. The antagonist profile of the muscarinic stimulation of [35S]GTPγS binding was highly correlated with that displayed by the muscarinic stimulation of adenylyl cyclase. These data indicate that the olfactory bulb muscarinic receptors couple to Gi/Go, but not to Gs, and support the possibility that activation of Gi/Go mediates the stimulatory effect on adenylyl cyclase activity.

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