m-35 and apraclonidine

The modulation of the central cardiovascular effects of alpha(2)-adrenoceptor activation by galanin and its N-terminal fragment galanin-(1-15) has been evaluated by quantitative receptor autoradiography and cardiovascular analysis. Intracisternal coinjections of threshold doses of galanin and the selective and hypotensive alpha(2)-receptor agonist clonidine induced rapid and 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 cardiovascular 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 [(3)H]p-Aminoclonidine binding sites in the nucleus tractus solitarii (NTS) compatible with a possible antagonistic interaction with the alpha(2)-adrenoceptors, and this effect was blocked by the presence of the specific galanin receptor antagonist M35. In addition, clonidine (30 nM) induced a 50% increase in the B(0) values of galanin based on competition experiments with [(125)I]-galanin binding in the NTS. These findings suggest the existence 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 binding. These mechanisms could be mediated by a reciprocal galanin-alpha(2) receptor interaction within the NTS.

Topics: Adrenergic alpha-Agonists; Animals; Autoradiography; Binding, Competitive; Blood Pressure; Bradykinin; Cardiovascular Physiological Phenomena; Clonidine; Dose-Response Relationship, Drug; Galanin; Kinetics; Male; Peptide Fragments; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-2; Receptors, Galanin; Receptors, Neuropeptide; Solitary Nucleus; Specific Pathogen-Free Organisms; Tritium