Phe—Met—Arg—Phe—NH₂ (FMRFa)-Related Peptides Inhibit Na/Ca Exchange in Pancreatic B Cells

Abstract

Two processes located at the cell plasma membrane appear to mediate Ca²⁺ extrusion from cells: the Ca²⁺ ATP ase and the process of Na/Ca exchange [1,2]. In the heart, Na/Ca exchange appears to be the predominant mechanism for Ca²⁺ extrusion, being able to restore and control basal Ca²⁺ level on a beat-to-beat basis [3]. Although the existence of a process of Na/Ca exchange in the pancreatic B cell has been postulated for many years, the process was only recently characterized and shown to regulate cytosolic free Ca²⁺ concentration within the physiological range. One major factor that has hindered rapid progresses in our knowledge of the process of Na/Ca exchange is the lack of specific inhibitors of the exchange. Recently, opioïd analogs (e.g. naloxone) were shown to inhibit Na/Ca exchange in cardiac sarcolemmal vesicles [4]. Likewise, peptides related to Phe— Met—Arg—Phe—NH₂ (FMRFa) with naloxone-like activity were observed to induce complete inhibition of Na/Ca exchange [5]. In addition, it was suggested that endogenous analogs of FMRFa may exert some of their physiological modulatory role by inhibiting Na/Ca exchange [5]. FMRFa is a molluscan peptide with potent effects on heart, as well as on other muscles and nerves of molluscs. FMRFa-related peptides have also been localized in several mammalian tissues and appear to exert various actions in eluding antagonism to opioïd analgesia [6,7]. The aim of the present study was to examine the effects of FMRFa-related peptides on Na/Ca exchange in rat pancreatic islet cells.