PT  - JOURNAL ARTICLE
AU  - Hsiang-en Wu
AU  - Kuei-chun Hung
AU  - Hirokazu Mizoguchi
AU  - James M. Fujimoto
AU  - Leon F. Tseng
TI  - Acute Antinociceptive Tolerance and Asymmetric Cross-Tolerance between Endomorphin-1 and Endomorphin-2 Given Intracerebroventricularly in the Mouse
DP  - 2001 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1120--1125
VI  - 299
IP  - 3
4099  - http://jpet.aspetjournals.org/content/299/3/1120.short
4100  - http://jpet.aspetjournals.org/content/299/3/1120.full
SO  - J Pharmacol Exp Ther2001 Dec 01; 299
AB  - Development of tolerance in mice pretreated intracerebroventricularly with μ-opioid receptor agonist endomorphin-1, endomorphin-2, or [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) was compared between endomorphin-1- and endomorphin-2-induced antinociception with the tail-flick test. A 2-h pretreatment with endomorphin-1 (30 nmol) produced a 3-fold shift to the right in the dose-response curve for endomorphin-1. Similarly, a 1-h pretreatment with endomorphin-2 (70 nmol) caused a 3.9-fold shift to the right for endomorphin-2. In cross-tolerance experiments, pretreatment with endomorphin-2 (70 nmol) caused a 2.3-fold shift of the dose-response curve for endomorphin-1, whereas pretreatment with endomorphin-1 (30 nmol) caused no change of the endomorphin-2 dose-response curve. Thus, mice acutely tolerant to endomorphin-1 were not cross-tolerant to endomorphin-2, although mice made tolerant to endomorphin-2 were partially cross-tolerant to endomorphin-1; an asymmetric cross-tolerance occurred. Pretreatment with DAMGO 3 h before intracerebroventricular injection of endomorphin-1, endomorphin-2, or DAMGO attenuated markedly the antinociception induced by endomorphin-1 and DAMGO but not endomorphin-2. It is proposed that two separate subtypes of μ-opioid receptors are involved in antinociceptive effects induced by endomorphin-1 and endomorphin-2. One subtype of opioid μ-receptors is stimulated by DAMGO, endomorphin-1, and endomorphin-2, and another subtype of μ-opioidreceptors is stimulated solely by endomorphin-2. The American Society for Pharmacology and Experimental Therapeutics