Muscarine Receptors Regulating Electrically Evoked Release of Acetylcholine in Hippocampus Are Linked to Pertussis Toxin-Sensitive G Proteins but Not to Adenylate Cyclase

Abstract: ³H]Acetylcholine release elicited with 360 pulses/3 Hz from slices of rabbit hippocampus is facilitated in the presence of the muscarine (M) receptor antagonist atropine (indicating the existence of autoinhibition) and diminished by the M receptor agonists carbachol and oxotremorine. W-Ethylmaleimide (30 μM ) and pertussis toxin (8 μg/ml) counteracted antagonist-induced facilitation and agonist-induced inhibition of release, suggesting that a pertussis toxin-sensitive GTP-binding protein is involved in the chain of events mediating activation of M receptors to inhibition of release. Neither 8-bromo-cyclic AMP (300 μM ), a membrane analogue of cyclic AMP, nor rolipram (10 μM ), a phosphodiesterase inhibitor, affected electrically evoked release of ³H]acetylcholine. They also did not influence the oxotremorine-induced inhibition of transmitter release. In conclusion, no evidence was found for the assumption that activation of M autoreceptors is linked to inhibition of adenylate cyclase.