Galanin/alpha2-receptor interactions in central cardiovascular control

The modulation of the central cardiovascular effects of alpha(2)-adrenocept or activation by galanin and its N-terminal fragment galanin-(1-15) has bee n evaluated by quantitative receptor autoradiography and cardiovascular ana lysis. intracisternal coinjections of threshold doses of galanin and the se lective and hypotensive alpha(2)-receptor agonist clonidine induced rapid a nd maintained vasopressor and tachycardic responses (p<0.001) instead of a hypotensive response, whereas the coinjections of threshold doses of the N- terminal galanin fragment (1-15) and clonidine did not elicit significant c ardiovascular changes. Receptor autoradiographical experiments showed that galanin (1 nM) significantly increased the K-d (p<0.01) and B-max values (p <0.01) of [H-3]-Aminoclonidine binding sites in the nucleus tractus solitar ii (NTS) compatible with a possible antagonistic interaction with the alpha (2)-adrenoceptors, and this effect was blocked by the presence of the speci fic galanin receptor antagonist M35. In addition, clonidine (30 nM) induced a 50% increase in the B-o values of galanin based on competition experimen ts with [I-125]-galanin binding in the NTS. These findings suggest the exis tence of an antagonistic effect of galanin, but not of galanin fragment (1- 15), on the cardiovascular responses mediated by alpha(2)-receptors as well as a reciprocal facilitatory effect of alpha(2)-receptors on galanin bindi ng. These mechanisms could be mediated by a reciprocal galanin-alpha(2) rec eptor interaction within the NTS. (C) 2000 Elsevier Science Ltd. All rights reserved.