Measurement of thermodynamic parameters for norepinephrine contraction of isolated rabbit thoracic aorta.
The thermodynamic quantities of change in free energy (delta G degree'), change in enthalpy (delta H degree') and change in entropy (delta S degree') were determined for the interaction of norepinephrine with the alpha-1 adrenoceptor of vascular smooth muscle. Specifically, a standard isolated rabbit thoracic-aorta preparation was used to examine the effect of temperature on norepinephrine-induced isometric tension development. Dissociation constants (KA) for norepinephrine were determined at several temperatures over the range 25-40 degrees C from equiactive concentrations obtained before (A) and after (A') partial irreversible receptor blockade by phenoxybenzamine, plotted as 1/A against 1/A' (KA = (slope-1)/intercept). The values of KA increased with temperature over the range 25-40 degrees C, indicating that the affinity of norepinephrine for the alpha-1 adrenoceptor is an inverse function of temperature over this range. From these results, the thermodynamic quantities delta H degree' and delta S degree' were determined from a van't Hoff plot of In (KA) against 1/T. The relative magnitudes of the change in enthalpy (delta H degree' = -25.58 kcal mol-1) and the change in entropy (delta S degree' = -0.052 kcal mol-1 deg-1) suggest that the reaction between norepinephrine and the alpha-1 adrenoceptor (delta G degree' = -9.15 kcal mol-1) is enthalpy driven, which is consistent with radioligand binding studies of other adrenoceptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013696:Temperature; D013816:Thermodynamics; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D009638:Norepinephrine