Thermodynamic analysis of beta-adrenergic partial agonists (befunolol and carteolol) interaction with low and high affinity binding sites of beta-adrenoceptors in guinea-pig taenia caecum.
1. Effects of temperatures (0, 10 and 32 degrees C) on the bindings of beta-adrenergic partial agonists, befunolol and carteolol, with beta-adrenoceptors were studied using the microsomal fractions from the guinea-pig taenia caecum. 2. The affinities of befunolol and carteolol to the low affinity binding site were higher at low temperatures, whereas those to the high affinity binding site were not influenced by change in temperature. 3. The interactions of the low affinity binding site with befunolol and carteolol decreased both enthalpy and entropy. The interactions of both the drugs with the high affinity binding site increased only entropy. 4. These results support our view that beta-adrenoceptors contain two different affinity binding sites and that the interactions of beta-adrenergic partial agonists with the low affinity binding site induce the beta-adrenomimetic action, whereas the competitive antagonism by the beta-partial agonists and beta-adrenoceptor blockers is due to their ability to compete with beta-stimulant for the high affinity binding site.
Takayanagi
I
I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Ogishima
M
M
Koike
K
K
D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002354:Carteolol / Q000378:metabolism* / Q000494:pharmacology; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000378:metabolism* / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013696:Temperature; D013816:Thermodynamics
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C006034:befunolol; D002354:Carteolol