Salicylates and Phospholipid Bilayer Membranes

Abstract

FERREIRA¹ has observed that pain receptors are sensitized by prostaglandins, which strongly supports his suggestion that aspirin-like drugs induce analgesia by blocking the synthesis of prostaglandins. Salicylates, however, also produce an increase in the permeability of a molluscan neurone to potassium and a decrease in the permeability of the neurone to chloride which Barker and Levitan^2–4 have suggested may be related to the analgesic action of the drugs. More extensive pharmacological investigations are obviously required to ascertain whether analgesia could be a membrane related phenomenon, and these studies would be facilitated by a knowledge of the molecular mechanism by which salicylates modify the permeability of neurones to electrolytes. A simple working hypothesis is that the “receptor site” of the neuronal membrane for salicylate is the ubiquitous⁵ phospholipid bilayer. An adsorption of salicylate anions to the bilayer would produce a negative electrostatic surface potential which would modify the inter-facial ion concentrations and thus give rise to the observed changes in permeability. If the hypothesis is correct, salicylate should produce similar effects on neurones and artificial phospholipid bilayer membranes. It does.