A STUDY OF THE ALTERATION IN RECEPTOR ACTIVITY OF THE RAT FUNDAL STRIP BY UREA

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

This study is an extension of our previous work, in which heat was used to characterize in a general way the molecular nature of drug receptors present in smooth muscle. In the present work the isolated rat stomach fundal strip was subjected to 2 M urea for 19 min. Dose-response curves to KCl and various receptor agonists were determined before and after urea treatment. Under these conditions, urea produced little or no effect on responses to KCl, indicating that the conducting membrane and contractile elements were unaffected. This treatment decreased the responsiveness of the tissue to a variety of drugs known to interact with specific receptors. The order of desensitization to urea was bradykinin acetylcholine serotonin angiotensin. These effects are attributed to an alteration in the structure of the active sites on the various receptors examined leading to a loss of biologic activity. These results suggest that the receptors for acetylcholine, bradykinin, serotonin and angiotensin are proteins. It is quite apparent that these proteins differ markedly from one another, as indicated by the striking differences in their stability to urea.