Dopamine D2 receptors in the posterior region of the nucleus tractus solitarius mediate the central pressor action of quinpirole (LY171555).
Our previous studies demonstrated that intravenous (IV) administration of the selective dopamine (DA) D2 receptor agonist quinpirole (LY171555) induces a pressor response in conscious Sprague-Dawley (S-D) rats through a central mechanism. The present study was designed to identify the neurons which medicate this pressor response. Injection of quinpirole (1-150 micrograms/kg) into the 4th ventricle produced a greater pressor response of a more rapid onset than similar injections into the lateral ventricle in conscious, freely moving S-D rats, suggesting a site of action in brainstem. Further, microinjections (5-10 micrograms/kg in 200 nl) of quinpirole into major hypothalamic nuclei of conscious, freely moving rats elicited no pressor response. Uni- or bilateral microinjections of quinpirole (5 micrograms/200 nl) into the posterior region of nucleus tractus solitarius (P-NTS) caused a consistent increase in mean arterial pressure (MAP) (Max = 12.4 +/- 1.1 mmHg, n = 12) with a rapid onset (less than 30 sec) in unanesthetized decerebrate S-D rats, while microinjections into the anterior region of NTS, area postrema, C1/A1 regions, raphe obscurus nucleus, locus coeruleus or regions 0.5 mm lateral, superior or inferior to P-NTS produced little or no response. The pressor response induced by bilateral microinjections of quinpirole into P-NTS was not different from that of unilateral microinjection. The pressor response to microinjection of quinpirole into P-NTS was abolished by pretreatment with metoclopramide (5 mg/kg, IV or 25 micrograms/200 nl, P-NTS injection; 5 min before), a selective DA D2 antagonist that crosses the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
R H
RH
Department of Medicine, University of Alabama, Birmingham 35294.
Igarashi
Y
Y
Wyss
J M
JM
Chen
Y F
YF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D004873:Ergolines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2
D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D019257:Quinpirole