1. Effect of PG-SPI and PG-KII, two novel and natural tachykinins, on salivary secretion in the rat
M Broccardo, G Improta, A Brandoni, A Tabacco Peptides. 1996;17(4):729-31. doi: 10.1016/0196-9781(96)00052-6.
In an in vivo study of salivation in rats, the scialogogic effects of two natural and amphibian tachykinins, PG-SPI and PG-KII, which activate distinct tachykinin receptors, were compared with those of the tachykinins substance P, neurokinin A and B, and kassinin. The rank order of potencies of these peptides injected intravenously on salivation was: PG-SPI = SP > or = PG-KII = KASS > NKA > > NKB. Atropine (1 mg/kg. i.v.) had no effect on PG-SPI-, SP-, and NKA-induced salivation, but reduced that stimulated by PG-KII and KASS. We conclude that PG-SPI and PG-KII increase salivary secretion through different mechanisms and that rat salivary glands contain PG-SPI-and PG-KII-sensitive receptors.
2. Stimulatory effect of PG-KII, an NK3 tachykinin receptor agonist, on isolated pancreatic acini: species-related differences
G Linari, G Improta, S Agostini, A Andreassi, M Broccardo Peptides. 2004 Jan;25(1):45-51. doi: 10.1016/j.peptides.2003.11.007.
More information is needed on the physiological role of the tachykinins (TKs), especially neurokinin3-receptor (NK3) agonists, in the pancreas. In this paper we investigated and compared the effect of PG-KII (10(-9) to 10(-6) M), a natural NK3-receptor agonist, with that of the known secretagogues substance P (10(-9) to 10(-6)M), caerulein (10(-11) to 10(-8) M) and carbachol (10(-8) to 10(-5) M), on amylase secretion from dispersed pancreatic acini of the guinea pig and rat. PG-KII (10(-7) M) significantly increased basal amylase release from guinea pig pancreatic acini (from 5.4+/-0.9% to 11.3+/-0.5%, P < 0.05) but left basal release in the rat unchanged (6.5+/-0.5%). The stimulant effect of PG-KII on guinea pig acini was significantly reduced by the NK3-receptor antagonist, SR 142801 (5 x 10(-7) M), and left unchanged by the NK1-receptor antagonist, SR 140333 (5 x 10(-7) M). Conversely, substance P (10(-7) M) significantly stimulated amylase secretion from rat and guinea pig acini (12.6+/-0.6% and 12.1+/-0.7%, P < 0.05). This stimulated effect of substance P was antagonized by the NK1--receptor antagonist (5 x 10(-7) M), but not by the NK3-receptor antagonist (5 x 10(-7) M). The PG-KII- and substance P-evoked maximal responses were lower than those evoked by caerulein (10(-9) M) (guinea pig, 19.1+/-1.3%; rat, 1802+/-0.9%, P < 0.01) and carbachol (10(-5) M) (guinea pig, 23.3+/-1.2%; rat, 24.0+/-1.1%, P < 0.01). The inhibitors of phospholipase C U-73122 (10(-5) M), phospholipase A2 quinacrine (10(-5)M), and protein tyrosine kinase genistein (10(-4) M), partly but significantly inhibited PG-KII, as well as carbachol-stimulated amylase release. Coincubation of PG-KII 10(-7) M with submaximal doses of caerulein (10(-11) to 10(-10) M) and carbachol (10(-7) to 10(-6) M) had an additive effect on amylase release. Pre-incubation with PG-KII (10(-7) M) for 30 min significantly reduced the subsequent amylase response to PG-KII, whereas pre-incubation with caerulein 10(-10) M or carbachol 10(-6) M did not. These findings suggest that PG-KII directly contributes to pancreatic exocrine secretion by interacting with acinar NK3 receptors of the guinea pig but not of the rat. PG-KII signal transduction involves the intracellular phospholipase C, phospholipase A2 and protein tyrosine kinase pathways. The NK3 receptor system cooperates with the other known secretagogues in regulating guinea pig exocrine pancreatic secretion and undergoes rapid homologous desensitization.
3. Further evidence that the tachykinin PG-KII is a potent agonist at central NK-3, but not NK-1, receptors
C Polidori, I Panocka, R Ciccocioppo, M Broccardo, G Improta, D Regoli, M Massi Peptides. 1997;18(6):825-33. doi: 10.1016/s0196-9781(97)00022-3.
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.
