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

Abstract

1 The e ects of two sigma (s) binding site ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), on bladder functions were examined in rats. 2 Cystometry using urethane-anaesthetized rats showed that (+)-pentazocine (1 ± 5 mg kg 71 , i.v.) and DTG (1 ± 5 mg kg 71 , i.v.) prolonged micturition intervals, indicating increased bladder capacity and raised the threshold pressure.3 The e ects of (+)-pentazocine (2 mg kg 71 , i.v.) on micturition were not in¯uenced by naloxone (0.5 mg kg 71 , i.v.), which antagonized similar e ects of morphine (2 mg kg 71 , i.v.). 4 When administered intracerebroventricularly (i.c.v.), DTG (1 mg) and (+)-pentazocine (30 mg) prolonged micturition intervals with increased threshold pressure on the cystometrogram. 5 In isolated bladder detrusor strips of rats, (+)-pentazocine (3 mM) and DTG (1 mM) did not a ect contractile responses to electrical ®eld stimulation. A higher concentration of DTG (3 mM) slightly suppressed the response induced by 30 Hz stimulation.6 The e ects of (+)-pentazocine and DTG on micturition were abolished by pre-treatment with pertussis toxin (PTX, 1 mg, i.c.v.). 7 These results indicate that typical s ligands, such as (+)-pentazocine and DTG, increase bladder capacity in anaesthetized rats. Moreover, the mechanism by which s ligands change the urinary storage properties in rats may involve pathways in which the function of Gi/o proteins is necessary.

Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

“…administration of naloxone also suggests that naloxone-induced changes in bladder compliance are unlikely to account for our results. Shimizu et al 30 also failed to find any influence of naloxone (0.5 mg/kg; i.v.) alone on various cystometric parameters and similar negative results have been reported in a conscious rat preparation.…”

Synaptic Connections between Endomorphin 2-Immunoreactive Terminals and μ-Opioid Receptor-Expressing Neurons in the Sacral Parasympathetic Nucleus of the Rat

“…In the rat, MOR are known to be involved in central opioid modulation of bladder motility at both the supraspinal and spinal sites [20], [46], [47], [48]. In the rat spinal cord, both pharmacological and behavioral studies have provided compelling evidence that inhibition of micturition is mediated by MOR [31], [49], [50]. Bladder contractions may be inhibited by the MOR exogenous agonist morphine in an isovolumetric rat model, and this effect is abolished by the intravenous administration of the MOR antagonist naloxone [21], further suggesting that MOR in the spinal cord is involved in the regulation of bladder function.…”

Effects of dextromethorphan on in vitro contractile responses of mouse and rat urinary bladders

“…Shimizu et al [2000Shimizu et al [ , 2001 showed that (þ)-pentazocine and 1,3-di-o-tolylguanidine (DTG) prolong micturition intervals, indicative of increased bladder capacity, and raised the threshold bladder pressure after either i.v. or i.c.v.…”

“…Dextromethorphan also exhibits relatively high a⁄nity for the sigma-1 receptor [Chou et al, 1999] and there is some evidence that sigma-1 receptors mediate its antitussive e⁄cacy [Brown et al, 2004]. Although relatively little is known about the role of sigma receptors in micturition, Shimizu et al [2000Shimizu et al [ , 2001 reported that sigma receptor agonists reduce the frequency of volume-induced bladder contractions, increase bladder capacity and raise the threshold pressure for micturition in anesthetized rats. Interestingly, the sigma receptor agonist 1,3-di-o-tolylguanidine also inhibits electrically stimulated contractions of isolated bladder strips in vitro [Shimizu et al, 2000].…”

“…Although relatively little is known about the role of sigma receptors in micturition, Shimizu et al [2000Shimizu et al [ , 2001 reported that sigma receptor agonists reduce the frequency of volume-induced bladder contractions, increase bladder capacity and raise the threshold pressure for micturition in anesthetized rats. Interestingly, the sigma receptor agonist 1,3-di-o-tolylguanidine also inhibits electrically stimulated contractions of isolated bladder strips in vitro [Shimizu et al, 2000]. The e¡ects of DXM on micturition [Tillig and Constantinou, 2003] could thus be caused by either blockade of NMDA receptors or activation of sigma-1 receptors.…”