Effects of (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), sigma (sigma) ligands, on micturition in anaesthetized rats

1 The effects of two sigma (sigma) binding site ligands, (+)-pentazocine an d 1,3-di-o-tolylguanidine (DTG), on bladder functions were examined in rats . 2 Cystometry using urerhane-anaesthelized rats showed that (+)-pentazocine (1-5 mg kg(-1), i.v,) and DTG (1-5 mg kg(-1). i.v.) prolonged micturition i ntervals, indicating increased bladder capacity and raised the threshold pr essure. 3 The effects of (+)-pentazocine (2 mg kg ', i.v.) on micturition were not influenced by naloxone (0.5 mg kg(-1), i.v.), which antagonized similar eff ects of morphine (2 mg kg(-1), i.v.). 4 When administered intracerebroventricularly (i.c.v), DTG (1 mu g) and (+) -pentazocine (30 mu g) prolonged micturition intervals with increased thres hold pressure on the cystometrogram. 5 In isolated bladder detrusor strips of rats, (;)-pentazocrine (3 mu M) an d DTG (1 mu M) did not affect contractile responses to electrical field sti mulation. A higher concentration of DTG (3 mu M) slightly suppressed the re sponse Induced by 30 Hz stimulation. 6 The effects of (+)-pentazocine and DTG on micturition were abolished by p re-treatment with pertussis toxin (PTX, 1 mu g, i.c.v.). 7 These results indicate that typical a ligands, such as (+)-pentazocine an d DTG, increase bladder capacity in anaesthetized rats. Moreover, the mecha nism by which sigma ligands change the urinary-storage properties in rats m ay involve pathways in which the function of Gi/o proteins is necessary.