Enhanced sensitivity of the iris sphincter to the muscarinic agonist carbachol at lower temperature

Cooling of the human iris sphincter from 37.5 degrees C to 17.5 degrees C potentiates the concentration response curves of the muscarinic agonist, carbachol. Although EC50 value 0.31 micromol/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 degrees C. Pretreatment of the tissue with competitive muscarinic receptor blocker, atropine, blocked the contractile action of carbachol at 37.5 degrees C and 17.5 degrees C which resulted in nearly equal KB of approximately 2 nmol/l, but at 17.5 degrees C, the contraction induced by carbachol was antagonized by atropine with difficulty to give pseudo KB of 67 nmol/l. Ideally, a competitive reversible antagonist is expected to give equal KB values for the drug receptor interaction; irrespective of the method of study. The higher KB value indicates a functional antagonism of the agonist activated cascade by the blocker. Clinical implications of the drug antagonism at low temperatures are discussed.