Effect of tachykinin NK2 receptor blockade on detrusor hyperreflexia induced by bacterial toxin in rats.

Abstract

PURPOSE:

To see whether a recently characterized model of bacterial toxin-induced urinary bladder inflammation (Stein et al., J. Urol. 155, 1133-1138, 1996) is associated with detrusor hyperreflexia, and whether endogenous tachykinins acting through NK2 or NK1 receptors were involved in this model.

MATERIALS AND METHODS:

The bladder of urethane-anesthetized male Wistar rats was cannulated through the dome. Intravesical administration of protamine sulfate (PS, 10 mg./ml./rat) or vehicle for 1 hour was followed by the intravesical administration of E. coli lipopolysaccharide (LPS, 1 mg./ml./rat) or vehicle for 1 hour. Cystometries (50 microl./min.) were performed 3.5 hours after the exposure to LPS. MEN 11,420, a peptide tachykinin NK2 receptor antagonist, was administered before cystometries or, in a separate group of animals, during cystometries. The effect of SR 140,333, a non-peptide NK1 receptor antagonist, was also assessed in the presence or absence of MEN 11,420. The urodynamic effects of PS + LPS were also tested in capsaicin-pretreated rats.

RESULTS:

Unlike PS or LPS alone, the intravesical administration of PS + LPS induced detrusor hyperreflexia. In PS + LPS treated animals during nonstop cystometries, the intermicturition interval was decreased by about 50% as compared to vehicle-pretreated rats. A quantitatively similar reduction in the bladder capacity was also observed. MEN 11,420 (100 nmol./kg., i.v.) restored the intermicturition interval in PS + LPS-pretreated rats at the level of controls by increasing the bladder capacity, whereas it had no effect in vehicle-pretreated rats. SR 140,333 (1 micromol./kg., i.v.) neither modified urodynamic parameters in controls and in PS + LPS-treated rats nor altered the effect of MEN 11,420 in these groups. Capsaicin pretreatment (164 micromol./kg., s.c., 4-5 days before) induced a two-fold increase of the bladder capacity in control rats and prevented PS + LPS-induced bladder hyperreflexia.

CONCLUSIONS:

The intravesical administration of PS + LPS produces the activation of capsaicin-sensitive afferents. Endogenous tachykinins released from these fibers act through NK2 receptors to induce detrusor hyperreflexia.

• Authors: A Lecci, M Tramontana, S Giuliani, M Criscuoli, C A Maggi
• Journal: The Journal of urology (J Urol) Vol. 160 Issue 1 Pg. 206-9 (Jul 1998) ISSN: 0022-5347 [Print] United States
• PMID: 9628651 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• MEN 11420
• Peptides, Cyclic
• Piperidines
• Protamines
• Quinuclidines
• Receptors, Tachykinin
• SR 140333

Topics

• Animals
• Escherichia coli
• Lipopolysaccharides
• Male
• Muscle, Smooth (drug effects, physiopathology)
• Peptides, Cyclic (pharmacology)
• Piperidines (pharmacology)
• Protamines (pharmacology)
• Quinuclidines (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Tachykinin (antagonists & inhibitors)
• Reflex, Abnormal (drug effects)
• Urinary Bladder (drug effects, physiopathology)