Galanin/alpha2-receptor interactions in central cardiovascular control.
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.
Díaz-Cabiale
Z
Z
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. ziada.diaz@neuro.ki.se
Narváez
J A
JA
Yanaihara
N
N
González-Barón
S
S
Fuxe
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019004:Galanin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014316:Tritium
D000316:Adrenergic alpha-Agonists; D010446:Peptide Fragments; D018341:Receptors, Adrenergic, alpha-2; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D014316:Tritium; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; C016986:apraclonidine; D019004:Galanin; D003000:Clonidine; D001920:Bradykinin