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

The effects of two sigma (sigma) binding site ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), on bladder functions were examined in rats. Cystometry using urethane-anaesthetized rats showed that (+)-pentazocine (1 - 5 mg kg(-1), i.v.) and DTG (1 - 5 mg kg(-1), i.v.) prolonged micturition intervals, indicating increased bladder capacity and raised the threshold pressure. The effects of (+)-pentazocine (2 mg kg(-1), i.v. ) on micturition were not influenced by naloxone (0.5 mg kg(-1), i.v. ), which antagonized similar effects of morphine (2 mg kg(-1), i.v.). When administered intracerebroventricularly (i.c.v.), DTG (1 microg) and (+)-pentazocine (30 microg) prolonged micturition intervals with increased threshold pressure on the cystometrogram. In isolated bladder detrusor strips of rats, (+)-pentazocine (3 microM) and DTG (1 microM) did not affect contractile responses to electrical field stimulation. A higher concentration of DTG (3 microM) slightly suppressed the response induced by 30 Hz stimulation. The effects of (+)-pentazocine and DTG on micturition were abolished by pre-treatment with pertussis toxin (PTX, 1 microg, i.c.v.). These results indicate that typical sigma ligands, such as (+)-pentazocine and DTG, increase bladder capacity in anaesthetized rats. Moreover, the mechanism by which sigma ligands change the urinary storage properties in rats may involve pathways in which the function of Gi/o proteins is necessary.