The effect of McN-A-343 and oxotremorine on acetylcholine (ACh) release and choline (Ch) transport was studied in corticocerebral synaptosomes of the guinea pig. The synaptosomes were preloaded with [3H]Ch after treatment with the irreversible cholinesterase inhibitor, diisopropyl fluorophosphate, and then tested for their ability to release isotope-labeled ACh and Ch in the presence and absence of these agents. The kinetics of release were determined at the resting state (basal release) and in the presence of 50 mM K+. Under either condition, McN-A-343 enhanced the release of isotope-labeled ACh, whereas oxotremorine inhibited the K(+)-evoked release but had no effect on the basal release. The enhancing effect of McN-A-343 on basal ACh release was fully blocked by the selective M1 muscarinic antagonist, pirenzepine (100 nM). In contrast to its enhancing effect on ACh release, McN-A-343 potently inhibited Ch efflux as well as Ch influx. These effects were not blocked by atropine, a nonselective muscarinic antagonist. Oxotremorine had no effect on Ch transport. Binding studies showed that McN-A-343 was 3.6-fold more potent in displacing radiolabeled quinuclidinyl benzilate from cerebral cortex muscarinic receptors (mostly M1 subtype) than from cerebellar receptors (mostly M2 subtype), whereas oxotremorine was 2.6-fold more potent in the cerebellum. The displacements of radio-labeled pirenzepine and cis-dioxolane confirmed the M1 subtype preference of McN-A-343 and the M2 subtype preference of oxotremorine.(ABSTRACT TRUNCATED AT 250 WORDS)

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1. Adenosine (0.1-1 mM) or its 5'-monophosphate (5'-AMP) induced a concentration-dependent relaxation of tension caused by acetylcholine (0.2 microM) in human urinary bladder detrusor strips. 2. This effect was antagonized concentration dependently by theophylline at an apparent pA2 value of about 5. 3. Maximum relaxation by adenosine or 5'-AMP never exceeded 50% and 80%, respectively, of acetylcholine-induced tension. Relaxation by some beta2-adrenoceptor agonists (0.1-0.2 mM) or norepinephrine was limited to about 50% of maximum. 4. The responses to adenosine and terbutaline were additive, causing full relaxation, and suggesting mobilization of distinct mechanisms underlying muscle relaxation.