Reciprocal interactions between alpha 2-adrenoceptor agonist and neuropeptide Y binding sites in the nucleus tractus solitarius of the rat. A biochemic and autoradiographic analysis.
Interactions between a alpha 2-adrenoceptor agonist and neuropeptide Y (NPY) binding sites have been studied in the rat medulla oblongata (MO) using biochemical binding techniques as well as quantitative autoradiography. Tritiated para-amino clonidine (3H-PAC; alpha 2-adrenoceptor agonist), idazoxan (3H-IDA; alpha 2-adrenoceptor antagonist) and iodinated neuropeptide Y (125I-NPY) were used as radioligands. (1) Neuropeptide Y (NPY; 10(-8) M) but not bovine pancreatic polypeptide (BPP) nor peptide YY (PYY 10 nM) increased the KD value of 3H-PAC binding sites. However, intraventricular administration of a high dose of NPY (1.25 nmol) did not change the 3H-PAC binding characteristics in MO membrane preparations of these animals. (2) GTP 10(-4) lowered the affinity of 3H-PAC binding. NPY (10 nM) had no additional effect, nor did NPY influence the GTP induced shift in potency of clonidine to displace 3H-IDA from its binding sites. (3) In the autoradiographical experiments NPY (10 nM) significantly reduced 3H-PAC binding (2 nM) in the nucleus tractus solitarius (NTS) area by 35%. (4) When clonidine, either given centrally in vivo (3.75 nmol) or in vitro (10 nM) the binding of 125I-NPY was reduced (34 and 24%, respectively) in the NTS. When the monoamine receptors were irreversibly blocked in vivo by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 micrograms i.c. 24 h) 125I-NPY (0.5 nM) binding was increased by 137% in the NTS. This effect of EEDQ was prevented by pretreatment with the alpha 2-adrenoceptor antagonist idazoxan. These results provide support for a direct intramembrane interaction between the alpha 2-receptor and the NPY receptor within the NTS and may be of importance in central cardiovascular regulation.
Härfstrand
A
A
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Fuxe
K
K
Agnati
L
L
Fredholm
B
B
D000818:Animals; D001667:Binding, Competitive; D003000:Clonidine / Q000031:analogs & derivatives* / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D019329:Idazoxan; D007700:Kinetics; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D004146:Dioxanes; D009478:Neuropeptide Y; D011804:Quinolines; D011942:Receptors, Adrenergic, alpha; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; C000470:EEDQ; C016986:apraclonidine; D003000:Clonidine; D019329:Idazoxan