Cholinergic receptor subtypes in the urinary bladder of the rat in situ

The published evidence on the contractile response of the isolated urinary bladder in vitro suggests that neurotransmission in the smooth muscle is complex. The present work attempts to characterize muscarinic receptor subtypes involved in the contractile response of the whole urinary bladder of the rat in situ, using selective muscarinic antagonists. The intra-arterial administration of acetylcholine (ACh, 0.001 - 3 mg/kg) or carbachol (CCh, 0.001 - 1 mg/kg) produced a dose-dependent contraction with EC₅₀ values (ACh: 0.028 mg/kg, CCh: 0.024 mg/kg) and E_max values not significantly different (2.02 ± 0.16 g for ACh, n = 46 and 1.86 ± 0.14 g for CCh, n = 48; P > 0.05). The pretreatment of the rat with the M₁ selective antagonist PZP (0.238, 0.714, 2.38 or 714 μM) produced an antagonism characterized by apparent pA₂ values of 6.77 ± 0.14 (n = 24) and 4.86 ± 0.28 (n = 28), for ACh and CCh, respectively. When the rat was pretreated with the M₃ selective antagonist, p-FHHSD (0.238, 0.783 and 2.61 μM), apparent pA₂ values of 6.07 ± 0.11 for ACh (n = 18) and 6.19 ± 0.48 (n = 20) for CCh were found. With the M₂ selective antagonist AFDX-116 (0.239, 0717 and 2.39 μM), the corresponding apparent pA₂values were 5.30 ± 0.19 (n = 24), in the case of ACh and 5.02 ± 0.31 (n = 22), in the case of CCh. The results obtained demostrate that ACh-induced contractile responses in the rat urinary bladder in situ are due mainly to the activation of ACh-M₁and ACh-M₃ receptor subtypes, while CCh contractile responses seem to be due to the activation of ACh-M₃ and/or ACh-M₂ receptor subtypes.