Inhibition of ATP‐Induced Contraction in the Guinea‐pig Urinary Bladderin Vitroandin Vivo

Contractions were elicted by adenosine 5'-triphosphate (ATP) in the guinea-pig urinary bladder in vitro and in vivo. In isolated detrusor strips, tetrodotoxin (3.1 x 10(-6)--4.4 x 10(-5) M) did not affect contractions induced by a submaximum concentration (10(-3) M) of ATP, nor did atropine (1.7 X 10(-6)--2.1 x 10(-4) M), or the anticholinergic agent PR 197 within the concentration range 2.6 x 10(-8)--2.6 x (0(-5) M. In higher concentractions (5.2 x 10(-5)--2.6 x 10(-4) M), PR 197 inhibited the ATP-response by 60-70% in a way that was not clearly concentration-related. Isoprenaline (10(-7)--2.0 x 10(-5) M) and noradrenaline (2.5 x 10(-6)--10(-4) M) reduced the ATP-induced contractions by up to 79%. The effects of the amines were abolished by propranolol (5.2 x 10(-6)--3.8 x 10(-5) M). Adenosine, 1.0--2.0 x 10(-2) M, reduced the ATP-response by about 50%; in lower concentrations, it had no effect. Nifedipine, 7.8 x 10(-7)--1.2 x 10(-5) M, reduced the responses by 15-79%. Indomethacin (less than 2.0 x 10(-4) M), and theophylline (2.0 x 10(-4) M) had no consistent effects on ATP-induced concentrations. Exposure of the preparations to a calcium-free medium reduced and abolished the ATP-response within 60 min. Intravenous injection of ATP (1-20 MG/KG) caused a rapid and transient increase in intravesical pressure in the anaesthetized guinea-pig. The effect of ATP (3 mg/kg) was reduced by atropine (5-10 mg/kg) by approximately 35%. PR 197 (2.5-5 mg/kg) abolished the ATP-response. Isoprenaline (5-100 microgram/kg) caused a 53-95% inhibition that could be blocked by propranolol (1 mg/kg). The inhibiting effect of noradrenaline (10-100 microgram/kg) could not be blocked by propranolol (1 mg/kg). Adenosine (1.5-3.0 mg/kg) given immedicately before ATP completely inhibited the ATP-response. Nifedipine, 0.1-0.2 mg/kg, reduced the ATP-induced contraction by 34 to 100%. It is concluded that the ATP-induced contraction is elicted by a direct effect on the smooth muscle cell. It can be inhibited non-specifically by drugs with different modes of action.