Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

Abstract

The properties of muscarinic acetylcholine␣receptors of porcine and human bladder detrusor were␣compared in radioligand binding studies using [³H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of␣muscarinic receptors was similar in male and female pigs and in humans (K _d = 35 ± 8 pM, B _max = 153 ± 30 fmol/mg protein). Atropine and subtype-selective antagonists had steep and monophasic competition curves in porcine and human detrusor with a rank order of potency of atropine ≫ hexahydro-sila-difenidol ≥ AF-DX 116 ≥ pirenzepine, indicating the presence of a␣homogeneous population of M₂ muscarinic receptors. In female pigs bladder outflow obstruction generated by partial urethral ligation or its surgical treatment by ileum augmentation or autoaugmentation did not significantly alter expression of muscarinic receptors or of α_2A-adrenoceptors, but the power was insufficient to exclude alterations of less than 60%. We conclude that porcine and human detrusor express muscarinic receptors of the M₂ subtype; despite these qualitative similarities the use of the porcine model may be limited by large biological variance with regard to quantitative receptor expression.