INVOLVEMENT OF SPINAL TACHYKININ NK1 AND NK2 RECEPTORS IN DETRUSOR HYPERREFLEXIA DURING CHEMICAL CYSTITIS IN ANESTHETIZED RATS

The intraperitoneal administration of cyclophosphamide (150 mg/kg, 48 h before cystometry) induced detrusor hyperreflexia in urethane-anaest hetized rats. Intrathecal administration of the selective tachykinin N K1 receptor antagonist, GR 82,334 o-gamma-lactam)Leu(10),Trp(11)]physa laemin-(1-11)) (1 nmol/rat i.t.) had no significant effect on micturit ion in normal rats but increased the volume threshold In cyclophospham ide-treated rats. Another tachykinin NK1 receptor antagonist, RP 67,58 0 no-2(2-methoxyphenyl)ethyl]perhydroisoindol-4-one) (10 nmol/rat i.t. ) increased the volume threshold to a similar extent in both vehicle- and cyclophosphamide-treated animals. The tachykinin NK2 receptor anta gonist, SR 48,968 lpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide h ydrochloride (10 nmol/rat i.t.) did not modify micturition parameters in normal rats but antagonized bladder hyperreflexia in cyclophosphami de-treated animals; SR 48,968 restored the volume threshold for the mi cturition reflex to values close to control values. SR 48,965 lpiperid ino)-2-(3,4-dichlorophenyl)butyl]benzamide hydrochloride) (10 nmol/rat i.t.), the enantiomer of SR 48,968 devoid of affinity for tachykinin NK2 receptors, was inactive. 2-Amino-5-phosphonovaleric acid (25 and 2 50 nmol/rat i.t.), a selective antagonist of NMDA receptors, augmented the volume threshold both in controls and in rats with detrusor hyper reflexia; after administration of this antagonist, however, the volume threshold in cyclophosphamide-treated animals was still lower than in controls. Intravenous administration of SR 48,968, RP 67,580, or the combined administration of SR 48,968 and RP 67,580 had no effect on cy stometry variables either in rats with detrusor hyperreflexia or in co ntrols. The present results indicate that tachykinin NK1 and NK2 recep tors located in the spinal cord are involved in bladder hyperreflexia caused by chemically induced cystitis.