Heterogeneous distribution of muscarinic receptors in the rabbit saphenous artery

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Abstract
1 The properties of the muscarinic receptors in the rabbit saphenous artery were determined from electrical and mechanical responses of smooth muscle cells produced by acetylcholine (ACh). The inhibitory action of atropine and pirenzepine on the ACh-induced responses was also studied. 2 ACh produced a transient hyperpolarization of the membrane and inhibited the noradrenaline (NA)-induced contraction. These effects of ACh were apparent only when the endothelial cells were intact. 3 The ACh-induced transient hyperpolarization was antagonized by atropine or pirenzepine, with similar potencies (the ID50 values were about 2 × 10−8 m for both antagonists). 4 The ACh-induced inhibition of the contraction to NA was antagonized by atropine more preferentially than by pirenzepine (the ID50 values were 2 × 10−8 m for atropine and 10−6 m for pirenzepine). 5 The excitatory junction potential (e.j.p.) evoked by perivascular nerve stimulation was inhibited by ACh (above 10−8 m). The ACh-induced inhibition of the e.j.p. was antagonized by atropine more preferentially than by pirenzepine (the ID50 values were 3 × 10−8 m for atropine and 6 × 10−6 m for pirenzepine). 6 It is concluded that in the rabbit saphenous artery, two subtypes of muscarinic receptor (M1 and M2) are located on the endothelial cells. Stimulation of each subtype releases a different substance, i.e., a hyperpolarizing substance (M1-subtype) or a relaxant substance (M2-subtype). In prejunctional nerve terminals, the muscarinic receptors responsible for inhibiting the release of transmitter substances are of the M2-subtype.