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OPIATE BINDING AND EFFECT IN ILEUM PREPARATIONS FROM NORMAL AND MORPHINE PRETREATED GUINEA‐PIGS
Author(s) -
COX B.M.,
PADHYA REKHA
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb08415.x
Subject(s) - etorphine , opiate , morphine , chemistry , (+) naloxone , pharmacology , endocrinology , medicine , guinea pig , ileum , receptor , opioid , biochemistry
1 Dose‐response curves for normorphine in the absence and presence of naloxone have been obtained from myenteric plexus‐longitudinal muscle strip preparations from normal and morphine pretreated guinea‐pigs. In addition, the high affinity stereospecific binding of [ 3 H]‐etorphine has been measured in homogenates of the same tissue. 2 Higher concentrations of normorphine were required to produce 50% inhibition of the electrically stimulated contractions of strip preparations from morphine pretreated animals. There was also an increase in the slope of linearized dose‐response curves in opiate‐tolerant preparations. Maximum opiate effect was unchanged, and responses to exogenous acetylcholine were not affected by the pre‐treatment. 3 There was a slight increase in the apparent equilibrium constant for naloxone after morphine pre‐treatment. 4 Tolerance to opiate effect was not accompanied by a change in the affinity or number of stereo‐specific binding sites for [ 3 H]‐etorphine. Hill plots of [ 3 H]‐etorphine binding in both control and morphine pretreated preparations gave slopes close to unity. 5 Most of these results can be explained by the assumption that in tolerant preparations, a certain fractional opiate receptor occupation threshold must be exceeded before opiate effects become apparent. It is suggested that the tissue adapts toward a threshold equivalent to the mean receptor occupancy attained during the period of opiate drug pretreatment.