'$ 0007-4888/00/0010-961$25.00 ©2000 Plenum Publishing Corporation PHARMACOLOGY AND TOXICOLOGY Effect of Temperature on Guinea Pig Urinary Bladder Contraction Mediated via P2X-Receptors A. U. Ziganshin, A. V. Rychkov, and L. E. Ziganshina Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny , Vol. 130, No. 10, pp. 407-410, October, 2000 Original article submitted February 16, 2000 In vitro experiments showed that P2X-receptor agonist α,β-methylene-ATP and electrical field stimulation in the presence of muscarinic and α-adrenoreceptors blockers induced con- tractile responses of isolated guinea pig bladder, which were more pronounced at 30 o C than at 37 o C or 42 o C. P2X-receptor antagonist pyridoxal-6-phosphate-2,4-disulfonic acid, pro- duced a more potent inhibitory effect on contractions induced by electrical field stimulation at 30 o C in comparison with that at 37 o C or 42 o C, while the contractions induced by α,β-me- thylene-ATP were similarly suppressed at all examined temperatures. Key Words: P2X-receptors; bladder; temperature dependence Department of Pharmacology, Kazan State Medical University ATP receptors (P2-receptors) were revealed in various tissues, the bladder of guinea pig included [1]. Acti- vation of these receptors with α,β-methylene-ATP, an agonist of P2X-receptors, or electric field induces pha- sic contractions, which are inhibited with P2X-recep- tor antagonists suramin and pyridoxal-6-phosphate- 2,4-disulfonic acid (PPADS) [6,12,13]. Most experi- ments with P2-receptors were carried out under standard physiological conditions; however, there is evidence that the responses mediated by P2-receptors depend on pH [7,10]. Our aim was to study the effect of tempe- rature on the contractile responses mediated by P2X- receptors. MATERIALS AND METHODS Guinea pigs weighing 350-550 g were euthanized and dehematized. The bladder was isolated, 2×10-mm smooth muscle preparations were prepared and placed in 10-ml thermostabilized vials to measure isomeric contraction. The tissue was rested under a load of 1 g for about 1 h to adapt to the medium. Electrical field stimulation (EFS) was performed with two platinum rings with a diameter of 2.5 mm, through which the muscle strip was threaded. The modified Krebs so- lution contained (in mM): 133 NaCl, 4.7 KCl, 16.3 NaHCO 3 , 0.6 MgCl 2 , 1.35 NaHPO 4 , 2.5 CaCl 2 , 7.8 C 2 H 12 O 6 , oxygenated with 95% O 2 and 5% CO 2 (pH 7.3-7.4). In EFS experiments, atropine (3×10 7 M) and phentolamine (10 6 M) were added. The contrac- tions were measured with an FSG-01 transducer (Lin- ton) coupled with a Biopack digitizer and imputed to PC. EFS was performed with a Grass S9 stimulator. The duration, amplitude, and frequency of pulses were 0.5 msec, 100 V, and 1-64 Hz, respectively. α,β-Me- thylene-ATP (10 8 -3×10 5 M) was added to vials, and after attaining the maximum contraction the prepara- tion was rapidly washed several times in fresh Krebs solution to prevent desensitization of P2X-receptors. All contractile responses were calculated as the per- centage of maximum response to KCl (240 mM), which was introduced into the solution at the end of the experiment. The temperature was regulated with a Techne TE-8A pump by changing the temperature of circula- ting fluid. In all experiments, the initial stages and ad- aptation were carried out at 37±1 o C. Two successive contractions induced by α,β-methylene-ATP (3×10 6 Bulletin of Experimental Biology and Medicine, Vol. 130, No. 10, October, 2000