Further evidence that central tachykinin NK-1 receptors mediate the inhibitory effect of tachykinins on angiotensin-induced drinking in rats.
The order of potency of tachykinin (TK) receptor agonists suggests that TK NK-1 receptors mediate their inhibitory effect on water intake induced by intracerebroventricular (i.c.v.) injection of angiotensin II (AngII) in rats. The present study was aimed at further evaluating which TK receptor subtype mediates the effect, using selective antagonists for the TK receptor subtypes. Pulse i.c.v. injection of the TK agonist neuropeptide gamma (NP gamma), 31-250 ng/rat, markedly inhibited AngII-induced water intake. The i.c.v. injection of the NK-1 receptor antagonist SR14033, 0.5 microgram/rat, significantly reduced, while 1 microgram/rat completely abolished the inhibitory effect of NP gamma, 125 ng/rat. The selective NK-2 receptor antagonist SR48968 and the selective NK-3 receptor antagonist R820 were devoid of any effect up to the i.c.v. dose of 2 micrograms/rat. On the other hand, i.c.v. injection of SR140333, 1 microgram/rat, did not increase drinking induced by i.c.v. injection of AngII, 0.1-10 ng/rat, and did not increase drinking in water sated or water deprived rats. The results of the present study confirm that central TKergic mechanisms inhibit AngII-induced drinking in rats, and provide further evidence that TK NK-1 receptors mediate the effect. Failure of i.c.v. injected SR 140333 to increase AngII-induced drinking, as well as water intake in sated or deprived rats suggests that brain NK-1 receptor mechanisms apparently do not exert a tonic control on AngII-induced drinking and, in general, on water intake in rats. From a pharmacological point of view, the inhibitory effect of TKs on the dipsogenic action of AngII can represent a functional test for activity at central NK-1 receptors in rats.
Polidori
C
C
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Italy. Polidori@cambio.unicam.it
Ciccocioppo
R
R
De Caro
G
G
Massi
M
M
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002404:Catheterization; D004326:Drinking / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D007267:Injections; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018039:Receptors, Tachykinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000145:classification; D015320:Tachykinins / Q000494:pharmacology
D001549:Benzamides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; C109443:R 820; D018040:Receptors, Neurokinin-1; D018039:Receptors, Tachykinin; D015320:Tachykinins; D000804:Angiotensin II; C059905:tachykinin neuropeptide gamma; C085215:SR 140333; C073839:SR 48968