Thermodynamic parameters for [D-Pen2,5]enkephalin at delta-opioid receptors in the mouse isolated vas deferens.
Dissociation constants (KA) for [D-Pen2,5]enkephalin (DPDPE) inhibition of the electrically evoked twitch of the mouse isolated vas deferens preparation (MVD) were calculated at five temperatures (25, 30, 34, 37 and 40 degrees C). These values were determined from the equiactive concentrations obtained before (A) and after (A') partial irreversible blockade of a fraction of the receptor population by beta-chlornaltrexamine (beta-CNA) plotted as (1/A') where KA = (slope -1)/intercept. The values of KA tended to increase (approximately doubled) over this temperature range, indicating that the affinity of DPDPE for the opioid delta receptor is an inverse function of temperature. From these results, thermodynamic parameters were calculated from a Van't Hoff plot of 1n(KA) against 1/T. The relative magnitudes of the change in enthalpy (delta Ho' = -6.67 kcal mol-1), the change in entropy (delta So' = +0.009 kcal mol-1 degrees K-1) and the change in free energy (delta Go' = -9.43 kcal mol-1) suggest that the interaction between DPDPE and the delta-opioid receptor in MVD is an exothermic exergonic reaction, predominantly enthalpy-driven and results in an increase in the entropy of the system.
Raffa
R B
RB
Drug Discovery Research, R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477.
Wild
K D
KD
Mosberg
H I
HI
Porreca
F
F
D000818:Animals; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics; D014649:Vas Deferens / Q000378:metabolism*
D004745:Enkephalins; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C017120:chlornaltrexamine; D020881:Enkephalin, D-Penicillamine (2,5)-