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

• Published in: British journal of pharmacology Vol. 131; no. 3; pp. 610 - 616
• Main Authors: Shimizu, Isao, Kawashima, Katsuyoshi, Ishii, Daisuke, Oka, Makoto
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2000; Nature Publishing
• Subjects: (+)‐pentazocine; Anesthesia; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Biological and medical sciences; cystometry; DTG; Electric Stimulation; Gi/o proteins; Guanidines - pharmacology; Ligands; Male; Medical sciences; micturition; Muscle Contraction - drug effects; Narcotic Antagonists - pharmacology; Narcotic Antagonists - therapeutic use; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pentazocine - pharmacology; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pertussis Toxin; Pharmacology. Drug treatments; Rats; Rats, Wistar; Receptors, sigma - metabolism; Syncope - chemically induced; Syncope - drug therapy; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Virulence Factors, Bordetella - pharmacology; σ binding sites; Bladder function; Agonist; Intravenous administration; Rat; Opioid receptor; Rodentia; Contractility; Sigma receptor; Molecular interaction; In vitro; Biological activity; Pentazocine; In vivo; Vertebrata; Mammalia; Urinary system; Micturition; Animal; Intracerebral administration; Inhibitor; Antagonist; Mechanism of action; G protein
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703593

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 μM) and DTG (1 μM) did not affect contractile responses to electrical field stimulation. A higher concentration of DTG (3 μM) 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