The Membrane Binding of Morphine, Diphenylhydantoin, and Tetrahydrocannabinol

Abstract

SE~RZAN, P., CLIAIJ-WOM;, M., and MOYYFN, S. 8972. The r-nicnabranc binding of morphine, diphenylhydantoin, and teirahydrocannabi~aol. Can. J . Physiol. Pharrnasol. 50, 1193-1200.The adsorption of rnorgshirae to guinea pig brain synaptosornc membranes and to human erythrocyte rncmbranes was found lo be passive, and unaffectec8 by time, tanperature, o~aabain, dinitrophenol, saponin, or ATP. ' Y' he mernbrane/buffer partition coefficient for niorphine was 35 (at low ionic strength) and i . 2 (at high ionic strength). The synaptosome membrane/buffer partition coefficient for diphenylk~ydaralclin was around 60 (at pH 8), while that for A()-tetrahydrocannabinol (THC) was around 380 (in the concentration range of around 10-"M). The partition cc>efficient for the latter dsug dropped by a factor of two G;. three with increasing drug col-mcentrations for both erythrocyte ghosts and synaptosomes; there may be two types of binding sitcs for THC. The minimu111Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Auckland on 12/07/14For personal use only.Fnc;. 4. A double reciprocal plot of thc data of Fig. 3 indicates that the points fall on a single line, suggesting that there is one set of binding sites h r diphenylhydantoin (at p H 10.5).Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Auckland on 12/07/14For personal use only.

Pharmacology of Marijuana

“…The accumulation of THC was not significantly different at 4° and 37°C, nor affected by ouabain or dinitrophenol (61). Partition coefficients between buffer and synaptosome membrane lie between 100 and 500, and for red cell ghosts bet ween 800 and 40; the coefficient falling as free THC concentration increased from 4 X 10-6 to 4 X 10-5 M (62). Tissue/medium concentration for brain cortex slices in vitro of about 100 had been reported earlier (63).…”

Mu Opioids and Their Receptors: Evolution of a Concept

“…The proposal of opioid receptors goes back many decades, first being proposed based upon the rigid structure-activity relationships of the opiates (Beckett andCasy, 1954, 1965;Beckett, 1956;Beckett et al, 1956a,b;Janssen et al, 1960Janssen et al, , 1966de Stevens, 1965;Portoghese, 1966Portoghese, , 1970Jacobson et al, 1970). However, they were not demonstrated experimentally until 1973 Simon et al, 1973;Terenius, 1973), after many unsuccessful attempts (Chernov and Woods, 1965;Ingoglia and Dole, 1970;Navon and Lajtha, 1970;Berkowitz and Way, 1971;Goldstein et al, 1971;Hug and Oka, 1971;Seeman et al, 1972;Clouet and Williams, 1973;Van Praag and Simon, 1966). Most used the concept of stereospecificity, looking at the difference in binding of active and inactive stereoisomers, as described by Goldstein et al (1971).…”

Temperature dependence of anesthetic effects on succinate oxidase activity in uncoupled submitochondrial particles

“…It is well known that anesthetics affect the physical and enzymological properties of biological membranes, but the molecular mechanisms by which these effects are induced are poorly understood. Reports from several laboratories have shown that anesthetics increase membrane fluidity [1][2][3], decrease membrane density and increase surface area [4], and lower the phase transition temperature of purified lipids [3 ]. Many examples of enzyme inhibition by anesthetics are available [4--7], as well as some cases in which enzyme activation was observed [7,8].…”