Inhibition of dynorphin-converting enzymes prolongs the antinociceptive effect of intrathecally administered dynorphin in the mouse formalin test

European Journal of Pharmacology
K Tan-NoK Kisara

Abstract

The effects of peptidase inhibitors on the antinociceptive induced by intrathecally (i.t.) administered by dynorphin A and dynorphin B in the mouse formalin test were examined. When administered i.t. 5 min before the injection of 0.5% formalin solution into the dorsal surface of a hindpaw, dynorphin A (0.5-2 nmol) and dynorphin B (2-8 nmol) produced a dose-dependent and significant reduction of the paw-licking response. Dynorphin A (2 nmol) and dynorphin B (8 nmol)-induced antinociception disappeared completely within 90 min and 60 min, respectively. p-Hydroxymercuribenzoate, a cysteine proteinase inhibitor, and phosphoramidon, and endopeptidase 24.11 inhibitor simultaneously administered with dynorphin A or dynorphin B. Significantly prolonged antinociception induced by both dynorphins. However, captopril, and angiotensin-converting enzyme inhibitor, bestatin (a general aminopeptidase inhibitor) and a serine proteinase inhibitor phenylmethanesulfonyl fluoride, were active. Dynorphin converting enzyme(s) transform dynorphin-related peptides to [Leu5]enkephalin and [Leu5]enkephalin-Arg6. Neither [Leu5]enkephalin nor [Leu5]enkephalin-Arg6, even at high dose (10 nmol), produced any antinociceptive effect. However, [Leu5[enkephalin...Continue Reading

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Feb 15, 2000·Pharmacology, Biochemistry, and Behavior·E M BrandaR M Quock
May 16, 2002·Clinical and Experimental Pharmacology & Physiology·Mauricy Alves da MottaMaria Teresa de Almeida Jansen Catanho
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Jun 12, 2020·Neuropharmacology·Kinga HartmanJerzy Silberring

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