Muscarinic Receptors on Endothelial Cells

Abstract

Until this decade, muscarinic acetylcholine receptors (mAChR) were generally treated as a homogeneous population of membrane bound glycoproteins. In 1980, differences between mAChR located in certain brain areas and ganglia and those located in the heart and ileum were reported and two subtypes of mAChR were proposed based on receptor affinity for the antagonist pirenzepine. Receptors with high affinity for pirenzipine (cerebral cortex, hippocampus, striatum and ganglia) were termed M₁ and those exhibiting lower affinity (found in the heart, intestinal smooth muscle, cerebellum and brainstem) were termed M₂ (Hammer et al., 1980; Hammer and Giachetti, 1982; Berrie et al., 1986). Pharmacological studies with recently developed organ- and subtype- specific antagonists suggest that the M₂ subtype can be further distinguished into M_2α, and M_2β subtypes located in the heart and ileum, respectively (Giachetti et al., 1986; Lambrecht et al., 1984; 1987; Bonner et al., 1987). More recent analysis of the genes encoding mAChR has clearly revealed at least 4 distinct receptor subtypes (Ml, M2, M3, M4; Figure 1) which are the products of different genes (Kubo et al., 1986; 1986a; Bonner et al., 1989; Peralta et al., 1989,1987a). M2 defined by genetic analysis corresponds to the M₂ receptor defined pharmacologically, while Ml, M3 and M4 mAChR demonstrate significant similarity in their affinity to agonists and antagonists and probably contribute to the pharmacologically-defined M₁ receptor population. (Peralta et al., 1987). A fifth muscarinic receptor gene has recently been described (M5; Bonner et al, 1988), although its expression has not been demonstrated in any tissue.