Further evidence that the tachykinin PG-KII is a potent agonist at central NK-3, but not NK-1, receptors.
Intracerebroventricular (i.c.v.) injection of tachykinins (TKs) inhibits ethanol intake and angiotensin II-induced water intake; the effects are apparently mediated by NK-3 and NK-1 receptors, respectively. The present study evaluated the effect of the TK PG-KII, a novel kassinin-like peptide isolated from the skin of the Australian frog Pseudophryne güntheri, in these in vivo tests for central activity. PG-KII, given by i.c.v. injection, potently inhibited alcohol intake in genetically selected alcohol-preferring rats, being about 3 times more potent than the selective NK-3 receptor agonist NH2-SENK. The dose of 100 ng/rat, that markedly inhibited ethanol intake, did not inhibit food intake and prandial drinking in food deprived rats, providing evidence that the effect of PG-KII on ethanol intake is behaviorally selective. The effect on ethanol intake was inhibited by i.c.v. injection of the NK-3 receptor antagonist R820, but was not modified by the NK-1 receptor antagonist SR 140333. PG-KII inhibited drinking induced by angiotensin II only at doses of 300 or 1000 ng/rat, being about 5 times less potent than the selective NK-1 receptor agonist [Sar9, Met(O2)11] substance P. These doses of PG-KII produced also marked increase in competing behaviors, such as grooming and locomotion. The dose of 1000 ng/rat evoked a general inhibition of the ingestive behavior, reducing also food intake. The i.c.v. injection of the NK-1 receptor antagonist SR 140,333 only slightly inhibited the effect of PG-KII on angiotensin II-induced drinking, while it markedly reduced that of [Sar9, Met(O2)11] substance P. These findings, in accordance with those of previous studies, indicate that PG-KII is endowed with marked activity at central NK-3 receptors, and low activity at NK-1 receptors.
Polidori
C
C
Department of Pharmacological sciences and Experimental Medicine, University of Camerino, Italy. polidori@cambio.unicam.it
Panocka
I
I
Ciccocioppo
R
R
Broccardo
M
M
Improta
G
G
Regoli
D
D
Massi
M
M
D000428:Alcohol Drinking; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000819:agonists*; D018042:Receptors, Neurokinin-3 / Q000819:agonists*; D013237:Stereoisomerism; D015320:Tachykinins / Q000008:administration & dosage / Q000494:pharmacology*
D064729:Neurokinin-1 Receptor Antagonists; C103114:PG-KII peptide; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; D000804:Angiotensin II; C085215:SR 140333; D011761:Pyrrolidonecarboxylic Acid