Species difference in the muscarinic receptors of thoracic aorta.

Muscarinic receptors in rabbit aortic membranes were characterized by binding assays using I-[3H]quinuclidinyl benzilate, and compared with muscarinic receptors in dog and bovine aortas. In the rabbit aortic membranes, I-[3H]quinuclidinyl benzilate specifically bound with high affinity (KD = 28.1 pM) to a single class of sites (maximum number of binding sites = 57.2 fmol/mg of protein) which have characteristics of muscarinic receptors. Drug competition curves indicated a single class of binding sites for antagonists (e.g., K1 = 160 nM for pirenzepine), but suggested the presence of two affinity binding sites (or states) for agonists (e.g., K1 = 8.29 nM and K2 = 0.32 microM for oxotremorine, respectively). I-[3H]quinuclidinyl benzilate also bound to a single class of sites in the membranes of dog and bovine aortas, with similar affinities to the case of rabbit aorta. But the maximum number of binding site values were significantly lower than the value in the rabbit aorta. Furthermore, bovine aorta exhibited a higher affinity (K1 = 8.7-22.3 nM) for pirenzepine, but a lower affinity (K1 = 0.62-1.46 microM) for oxotremorine, as compared with rabbit and dog aortas. Accordingly, muscarinic receptors in the aorta are different between animal species, regarding its density and interactions with muscarinic agents. The receptors in bovine aorta may be M1-subtype but receptors in rabbit and dog aortas may be relatively M2-subtypes.