Effects of alkanols and halothane on rat brain muscarinic and alpha-adrenergic receptors.
Effects of the primary alcohols ethanol, butanol, pentanol and of halothane were measured on the binding functions of muscarinic and alpha-adrenergic receptor preparations in rat brain homogenates, with the use of the antagonists 3H-quinuclidinyl benzilate and 3H-WB-4101. IC50 concentrations of the alkanols for the muscarinic and alpha-receptors respectively were: ethanol, 2.0 M and 1.4 M; butanol, 0.24 M and 0.16 M; heptanol, 3.7 X 10(-3) M and 2.6 X 10(-3) M. The plot of IC50 values versus number of carbon atoms in the alkanol was linear and of the same slope as the plot of membrane fluidity changes, thus indicating the importance of the membrane/water partition coefficient of the alkanol. Halothane at clinical concentrations had no effect on the receptors, although significant inhibition of radioligand binding was produced by 2.5 mM halothane, and inhibition was complete in presence of 17.5 mM anesthetic. From the correlation of receptor binding inhibitions with membrane fluidity changes reported by other workers, it is suggested that the activity of membrane receptors may be modulated by the fluidity of their membranes.
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008024:Ligands; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000438:Alcohols; D008024:Ligands; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D006221:Halothane