Antagonistic regulation of alpha 2-adrenoceptors by neuropeptide Y receptor subtypes in the nucleus tractus solitarii.
The modulation of alpha 2-adrenoceptors by neuropeptide Y Y1 and neuropeptide Y Y2 receptor subtypes has been studied in the nucleus tractus solitarii of the male rat. The autoradiographical experiments showed that neuropeptide Y-(1-36), neuropeptide Y-(13-36), a selective neuropeptide Y Y2 receptor agonist, and [Leu31,Pro34]neuropeptide Y, a selective neuropeptide Y Y1 receptor agonist, in the nanomolar range increased the Kd value of the [3H]p-aminoclonidine binding sites in the above rank order of potency without changing the Bmax values. In contrast, in the competition experiments, the neuropeptide Y Y1 and the neuropeptide Y Y2 receptor agonists decreased and increased, respectively, with the same potency the IC50 value of l-adrenaline and especially of clonidine for the alpha 2-adrenoceptor agonist binding sites associated with an increase and a decrease of the B0 value, respectively. Cardiovascular experiments showed that microinjections of clonidine into the nucleus tractus solitarii induced dose-dependent vasodepressor and bradycardiac responses. Threshold doses for vasodepressor effects of neuropeptide Y-(1-36) and of the neuropeptide Y Y1 receptor agonist and for vasopressor effects of the neuropeptide Y Y2 receptor agonist significantly counteracted the vasodepressor action elicited by an ED50 dose of clonidine in the nucleus tractus solitarii, the bradycardiac action of clonidine also being counteracted by the neuropeptide Y Y2 but not the neuropeptide Y Y1 receptor agonist. The present results give indications for the existence of an antagonistic modulation of high affinity alpha 2-adrenoceptors by the neuropeptide Y Y1 and neuropeptide Y Y2 receptor subtype in the nucleus tractus solitarii which may contribute to a reduction of alpha 2-adrenoceptor-mediated cardiovascular depression.
Yang
S N
SN
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Fior
D R
DR
Hedlund
P B
PB
Agnati
L F
LF
Fuxe
K
K
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008297:Male; D009478:Neuropeptide Y / Q000819:agonists / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D017552:Solitary Nucleus / Q000033:anatomy & histology / Q000502:physiology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; D003000:Clonidine