Selective modulation of the NPY receptors of the Y2 subtype by alpha 2 receptors in the nucleus tractus solitarii of the rat. A cardiovascular and quantitative receptor autoradiographical analysis.
The modulation of neuropeptide Y (NPY) receptors by alpha 2 receptors in the nucleus tractus solitarii (Sol) of the rat was evaluated using quantitative receptor autoradiography and measurements of mean arterial blood pressure and heart rate. The receptor autoradiographical experiments showed that clonidine (10 nM), a selective alpha 2 receptor agonist, induced a 59% increase in the B0 value and a 47% decrease in the IC50 value of NPY(1-36) when competing for [125I]peptide YY ([125I]PYY)-binding sites in the presence of [Leu31, Pro34]NPY (100 nM), a selective NPY Y1 receptor agonist, to block the binding to NPY Y1 receptors. In contrast, when NPY(13-36) (300 nM), a selective NPY Y2 receptor agonist, was used to block the binding to NPY Y2 receptors, clonidine (1-30 nM) did not affect the B0 value and the IC50 value of NPY(1-36) when competing for [125I]PYY-binding sites, suggesting that the stimulation of alpha 2 receptors can selectively increase the affinity of NYP(1-36) for the NPY Y2 receptor. Microinjections of threshold doses of adrenaline or clonidine into the Sol not only counteracted the vasopressor action of a close to ED50 dose of coinjected NPY(13-36), but also changed the vasopressor and tachycardic response produced by NPY(13-36) into a vasodepressor and bradycardic response. However, threshold doses of adrenaline or of clonidine microinjected into the Sol did not modify the vasodepressor responses to a close to ED50 dose of NPY(1-36) or of [Leu31, Pro34]NPY.(ABSTRACT TRUNCATED AT 250 WORDS)
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
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism*; D017552:Solitary Nucleus / Q000033:anatomy & histology / Q000378:metabolism*
D007457:Iodine Radioisotopes; D018341:Receptors, Adrenergic, alpha-2; D017476:Receptors, Neuropeptide Y; D003000:Clonidine; D004837:Epinephrine