Muscarinic receptors discriminated by pirenzepine are involved in the regulation of neurotransmitter release in rat nucleus accumbens

Abstract

1 The effect of pirenzepine, a selective muscarinic antagonist, was tested on the oxotremorine facilitation of the K⁺-evoked release of [¹⁴C]-dopamine from tissue slices of rat nucleus accumbens. 2 The effect of pirenzepine was compared with that of scopolamine and other antagonists which show no heterogeneity in their action on muscarinic receptors in order to determine whether a selective action at a single receptor subtype, M₁ or M₂, could be distinguished. 3 Pirenzepine and scopolamine both antagonized the oxotremorine-induced (EC₅₀ = 3 × 10⁻⁷M) facilitation of [¹⁴C]-dopamine release with pA₂ values of 7.5 and 8.9 respectively. This result indicated that the high affinity pirenzepine receptor (M₁) was involved in this response. Low concentrations of 3-quinuclidinyl benzilate (3 × 10⁻¹⁰ M), N-methylscopolamine (3 × 10⁻⁹M) and methyl atropine (10⁻⁸ M) also abolished this facilitatory effect of oxotremorine.