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Inflammation modifies the role of cyclooxygenases in the contractile responses of the rat detrusor smooth muscle to kinin agonists.
J Pharmacol Exp Ther. 1998 Oct; 287(1):137-43.JP

Abstract

The contractile responses elicited by the selective kinin B1 and B2 receptor agonists [desArg9]-bradykinin ([desArg9]-BK) and [Hyp3, Tyr(Me)8]-bradykinin ([Hyp3, Tyr(Me)8]-BK) (1 nM-10 microM), respectively, were evaluated in control vs. inflamed (cyclophosphamide 150 mg kg-1 i.p., 48 h before the sacrifice) rat isolated urinary bladder strips. The contractile responses to the B2 receptor agonist did not differ in control vs. inflamed bladders, whereas the contractile responses to [desArg9]-BK were potentiated in inflamed bladders. The selective B1 and B2 receptor antagonists B 9858 (H-Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-OH) and Hoe 140 (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH), both at 1 microM, inhibited the response to the B1 and B2 receptor agonists, respectively, in both control and inflamed bladders. In addition, the concentration-response curve to [Hyp3, Tyr(Me)8]-BK was shifted to the right and depressed by B 9858 in inflamed bladders. The nonselective cyclooxygenase (COX) inhibitors S-(-)-ketoprofen (10 microM) and piroxicam (30 microM) markedly depressed the concentration-response curves to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in control bladders, but neither drug affected the B1 or B2 receptor agonist-mediated responses in inflamed bladders. The selective inhibitor of the inducible COX-2 isoenzyme, NS-398 (1 microM), did not inhibit the contractile responses to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in either control or inflamed bladders, whereas it significantly potentiated the response to the B1 receptor agonist in inflamed bladders. The exogenous administration of prostaglandin E2 (PGE2) induced S-(-)-ketoprofen-resistant contractile responses that were depressed in inflamed bladders. Pretreatment with S-(-)-ketoprofen restored the PGE2-mediated contractile responses of inflamed bladders to control values. PGE2 assay revealed that the basal production of PGE2 is significantly higher after inflammation than in control conditions. [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK (1 microM each) both stimulated PGE2 production, and their effect was larger in inflamed than in control bladders. Piroxicam (30 microM) prevented the PGE2 production evoked by [desArg9]-BK in both control and inflamed bladders and likewise abolished that produced by [Hyp3, Tyr(Me)8]-BK. NS-398 (1 microM) reduced the PGE2 production elicited by [desArg9]-BK in control and inflamed bladders. When NS-398 was tested on the [Hyp3, Tyr(Me)8]-BK-induced PGE2 production, it inhibited PGE2 production in the inflamed bladders only, without significantly modifying the response obtained in controls. These findings demonstrate that 1) in normal bladders, the activation of B1 and B2 receptors evokes contraction that is largely mediated by COX-1 metabolites, whereas the COX-2 appears to be involved in PGE2 production after the activation of B1 receptor only, without interfering with contraction, and 2) in inflamed bladders, the activation of B1 and B2 receptors still produce PGE2, but the contractile response is not reduced by COX inhibitors, a result that indicates that additional mechanisms play a compensatory role.

Authors+Show Affiliations

Pharmacology Department, Menarini Ricerche S.p.A., Florence, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9765332

Citation

Meini, S, et al. "Inflammation Modifies the Role of Cyclooxygenases in the Contractile Responses of the Rat Detrusor Smooth Muscle to Kinin Agonists." The Journal of Pharmacology and Experimental Therapeutics, vol. 287, no. 1, 1998, pp. 137-43.
Meini S, Lecci A, Cucchi P, et al. Inflammation modifies the role of cyclooxygenases in the contractile responses of the rat detrusor smooth muscle to kinin agonists. J Pharmacol Exp Ther. 1998;287(1):137-43.
Meini, S., Lecci, A., Cucchi, P., Catalioto, R. M., Criscuoli, M., & Maggi, C. A. (1998). Inflammation modifies the role of cyclooxygenases in the contractile responses of the rat detrusor smooth muscle to kinin agonists. The Journal of Pharmacology and Experimental Therapeutics, 287(1), 137-43.
Meini S, et al. Inflammation Modifies the Role of Cyclooxygenases in the Contractile Responses of the Rat Detrusor Smooth Muscle to Kinin Agonists. J Pharmacol Exp Ther. 1998;287(1):137-43. PubMed PMID: 9765332.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammation modifies the role of cyclooxygenases in the contractile responses of the rat detrusor smooth muscle to kinin agonists. AU - Meini,S, AU - Lecci,A, AU - Cucchi,P, AU - Catalioto,R M, AU - Criscuoli,M, AU - Maggi,C A, PY - 1998/10/9/pubmed PY - 1998/10/9/medline PY - 1998/10/9/entrez SP - 137 EP - 43 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 287 IS - 1 N2 - The contractile responses elicited by the selective kinin B1 and B2 receptor agonists [desArg9]-bradykinin ([desArg9]-BK) and [Hyp3, Tyr(Me)8]-bradykinin ([Hyp3, Tyr(Me)8]-BK) (1 nM-10 microM), respectively, were evaluated in control vs. inflamed (cyclophosphamide 150 mg kg-1 i.p., 48 h before the sacrifice) rat isolated urinary bladder strips. The contractile responses to the B2 receptor agonist did not differ in control vs. inflamed bladders, whereas the contractile responses to [desArg9]-BK were potentiated in inflamed bladders. The selective B1 and B2 receptor antagonists B 9858 (H-Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-OH) and Hoe 140 (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH), both at 1 microM, inhibited the response to the B1 and B2 receptor agonists, respectively, in both control and inflamed bladders. In addition, the concentration-response curve to [Hyp3, Tyr(Me)8]-BK was shifted to the right and depressed by B 9858 in inflamed bladders. The nonselective cyclooxygenase (COX) inhibitors S-(-)-ketoprofen (10 microM) and piroxicam (30 microM) markedly depressed the concentration-response curves to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in control bladders, but neither drug affected the B1 or B2 receptor agonist-mediated responses in inflamed bladders. The selective inhibitor of the inducible COX-2 isoenzyme, NS-398 (1 microM), did not inhibit the contractile responses to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in either control or inflamed bladders, whereas it significantly potentiated the response to the B1 receptor agonist in inflamed bladders. The exogenous administration of prostaglandin E2 (PGE2) induced S-(-)-ketoprofen-resistant contractile responses that were depressed in inflamed bladders. Pretreatment with S-(-)-ketoprofen restored the PGE2-mediated contractile responses of inflamed bladders to control values. PGE2 assay revealed that the basal production of PGE2 is significantly higher after inflammation than in control conditions. [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK (1 microM each) both stimulated PGE2 production, and their effect was larger in inflamed than in control bladders. Piroxicam (30 microM) prevented the PGE2 production evoked by [desArg9]-BK in both control and inflamed bladders and likewise abolished that produced by [Hyp3, Tyr(Me)8]-BK. NS-398 (1 microM) reduced the PGE2 production elicited by [desArg9]-BK in control and inflamed bladders. When NS-398 was tested on the [Hyp3, Tyr(Me)8]-BK-induced PGE2 production, it inhibited PGE2 production in the inflamed bladders only, without significantly modifying the response obtained in controls. These findings demonstrate that 1) in normal bladders, the activation of B1 and B2 receptors evokes contraction that is largely mediated by COX-1 metabolites, whereas the COX-2 appears to be involved in PGE2 production after the activation of B1 receptor only, without interfering with contraction, and 2) in inflamed bladders, the activation of B1 and B2 receptors still produce PGE2, but the contractile response is not reduced by COX inhibitors, a result that indicates that additional mechanisms play a compensatory role. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9765332/Inflammation_modifies_the_role_of_cyclooxygenases_in_the_contractile_responses_of_the_rat_detrusor_smooth_muscle_to_kinin_agonists_ DB - PRIME DP - Unbound Medicine ER -