THERMAL ALTERATION IN RECEPTOR ACTIVITY OF THE RAT FUNDAL STRIP

¹ Department of Pharmacology, Georgetown University Medical and Dental Schools, Washington, D.C.

The objective of this study was to use a physical method in an attempt to characterize the molecular nature of drug receptors in situ. The isolated rat stomach fundus strip was heated at various temperatures for various times. Dose-response curves to KCl and a number of receptor agonists were determined before and after heating. The experimental dose-response data were obtained after reequilibrating the tissue at the control temperature (37.5°C). Optimal conditions for achieving differential thermal effects were 47°C for 20 mm. KC1-induced contractions were unaffected, as were those to acetylcholine and bradykinin. A marked decrease in slope of the serotonin dose-response curve was produced. Although the maximum contraction height could be attained, this required a 1250-fold higher concentration than the control. Dose-response curves to angiotensin and vasopressin were affected to the greatest degree, showing a marked decrease in slope and a greatly depressed maximum contraction height. The simplest interpretation for the depressed responses is that heat caused an alteration in the structure of the active site on the various receptors. The comparatively mild conditions producing these effects suggest that the heat-labile receptors are composed entirely or in part of protein molecules which undergo irreversible heat denaturation.