Localization of AT(2) receptors in the nucleus of the solitary tract of spontaneously hypertensive and Wistar Kyoto rats using [125I] CGP42112: upregulation of a non-angiotensin II binding site following unilateral nodose ganglionectomy.
We have examined the binding distribution of a selective AT(2) receptor ligand [125I] CGP42112 in the brain of adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). AT(2) receptor localization was also examined in the rat brainstem following unilateral nodose ganglionectomy. Specific [125I] CGP42112 binding was observed in discrete brain regions from both rat strains, including the nucleus of the solitary tract (NTS), and did not differ between WKY and SHR. [125I] CGP42112 binding in the NTS revealed an AT(2) receptor component that was displaceable by PD 123319 and Ang II (50-58%), as well as a non-angiotensin II receptor component (42-49%). Following unilateral nodose ganglionectomy, [125I] CGP42112 binding density on the denervated side of the NTS was increased approximately two-fold in both WKY and SHR. This increased [125I] CGP42112 binding density in the ipsilateral NTS was comprised of a greater non-angiotensin II component than that observed in the sham groups, since only approximately 30% was displaced by PD123319 and angiotensin II. Furthermore, [125I] CGP42112 also revealed high binding density on the denervated side in the dorsal motor nucleus and the nucleus ambiguus in both WKY and SHR. AT(2) receptor immunoreactivity was also visualised in the NTS of sham operated rats, but was not observed in the dorsal motor nucleus or the nucleus ambiguus, nor was it up-regulated following nodose ganglionectomy. These results demonstrate, for the first time, an AT(2) receptor binding site in the NTS, as well as a non-angiotensin II [125I] CGP42112 binding site. These studies also demonstrate that nodose ganglionectomy represents a useful model in which to study a non-angiotensin II [125I] CGP42112 binding site that is up-regulated following degeneration of afferent vagal nerves.
Roulston
Carli L
CL
Department of Pharmacology, Monash University, 3800, Victoria, Australia.
Lawrence
Andrew J
AJ
Jarrott
Bevyn
B
Widdop
Robert E
RE
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D015171:Ganglionectomy / Q000379:methods; D007093:Imidazoles / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D019808:Losartan / Q000493:pharmacokinetics; D008297:Male; D009620:Nodose Ganglion / Q000601:surgery; D009842:Oligopeptides / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017552:Solitary Nucleus / Q000378:metabolism* / Q000503:physiopathology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D011725:Pyridines; D019275:Radiopharmaceuticals; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D019808:Losartan