title: Further evidence that the tachykinin PG-KII is a potent agonist at central NK-3, but not NK-1, receptors.
abstract: 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.
authors.affiliation: Department of Pharmacological sciences and Experimental Medicine, University of Camerino, Italy. polidori@cambio.unicam.it
authors.forename: C
authors.initials: C
authors.lastname: Polidori
authors.forename: I
authors.initials: I
authors.lastname: Panocka
authors.forename: R
authors.initials: R
authors.lastname: Ciccocioppo
authors.forename: M
authors.initials: M
authors.lastname: Broccardo
authors.forename: G
authors.initials: G
authors.lastname: Improta
authors.forename: D
authors.initials: D
authors.lastname: Regoli
authors.forename: M
authors.initials: M
authors.lastname: Massi
mesh_terms: 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*
chemical_list: 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