ABSTRACT

Adrenom edullin , originally isolated from h u m an phaeochrom ocytom as in 1993,1 is the m ost recently discovered m em ber o f the calciton in fam ily o f p ep tides .2 I t has som e sequence and s tru c tu ra l hom ology w ith a m y lin a n d C G R P in c lu d in g an N -term ina l six m em bered ring form ed by an in tra m o le c u la r d isu lp h id e b r id g e .1 A drenom edu llin p ep tide an d m RNA are w idely distributed w ith high concentrations in adrenal m edulla, lung, heart, spleen and kidney.3,4 Particularly high mRNA levels are present in endothelial and vascular sm ooth m uscle cells5,6 bu t the pep tide is also found in th e C N S .7 M an y fu n c tio n s , m a in ly card iovascu la r, have b een p ro p o sed for ad renom edu llin . T he m ost im p o rta n t o f these is probably a pow erful long-lasting vasodila tor response, sim ilar to CGRP.2,8 A drenom edullin also stim ulates o r inhibits cell grow th depending on cell type9 and has a num ber o f effects on salt and w ater bal­ ance.10 The m ain aim s o f ou r study were; a) to determ ine the d istrib u tio n o f ad ren o ­ m edullin b ind ing sites in tissues and differ­ en t m am m als and to com pare these w ith CGRP receptor d istribu tion , b) to ascertain w hether specific adrenom edullin receptors exist and to com pare the ir pharm acology w ith CGRP receptors. The results o f these

studies show ed the presence o f adreno - m edullin receptors in skeletal muscle and in this chapter we will also present som e data on the function and mechanism o f action of adrenom edullin in this tissue.