Enhanced Sensitivity of the Iris Sphincter to the Muscarinic Agonist Carbachol at Lower Temperature

Abstract

ABSTRACT

Cooling of the human iris sphincter from 37.5°C to 17.5°C potentiates the concentration response curves of the muscarinic agonist, carbachol. Although EC₅₀ value 0.31 μmol/l of the agonist was not significantly affected at the lower temperature, the maximum contraction of the control at 37.5°C was potentiated by 263%. Such potentiation was 272%, 135% and 125% for the dog, horse and pig in sphincter, respectively. Low temperature potentiation of the carbachol can be reversed by warming the tissue to 37.5°C Pretreatment of the tissue with competitive muscarinic receptor blocker, atropine, blocked the contractile action of carbachol at 37.5°C and 17.5°C which resulted in nearly equal K_B of ∼ 2 nmol/l, but at 17.5°C, the contraction induced by carbachol was antagonized by atropine with difficulty to give pseudo K_B of 67 nmol/l. Ideally, a competitive reversible antagonist is expected to give equal K_B values for the drug receptor interaction; irrespective of the method of study. The higher K_B value indicates a functional antagonism of the agonist activated cascade by the blocker. Clinical implications of the drug antagonism at low temperatures are discussed.