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

The effects of two sigma (σ) 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 μg) and (+)‐pentazocine (30 μg) prolonged micturition intervals with increased threshold pressure on the cystometrogram. In isolated bladder detrusor strips of rats, (+)‐pentazocine (3 μ M ) and DTG (1 μ M ) did not affect contractile responses to electrical field stimulation. A higher concentration of DTG (3 μ M ) 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 μg, i.c.v.). These results indicate that typical σ ligands, such as (+)‐pentazocine and DTG, increase bladder capacity in anaesthetized rats. Moreover, the mechanism by which σ ligands change the urinary storage properties in rats may involve pathways in which the function of Gi/o proteins is necessary.British Journal of Pharmacology (2000) 131 , 610–616; doi: 10.1038/sj.bjp.0703593