Inhibitory Action Of Neuropeptide Research Articles

Is neuropeptide Y responsible for constitutional delay of puberty in girls? A preliminary report

Constitutional delay of puberty (CDP) in otherwise healthy girls is defined as failure to develop secondary sexual features past the age of 13 years (two standard deviations above the mean age at which secondary sexual features appear in the population of girls). The inhibitory action of neuropeptide Y (NPY) on the gonadotropic and somatotropic systems in experimental animals and stimulation by NPY of the hypothalamic–pituitary–adrenal axis have been reported, prompting us to study the levels of NPY, insulin-like growth factor-I (IGF-I) and cortisol in eight girls with CDP and normal weight (body mass index (BMI) 21.7 ± 4.5 kg/m2). The results were compared with those from a group of 40 girls (BMI = 20.0 ± 3.1 kg/m2) who demonstrated a normal course of puberty (NP). All girls were studied at menarche (mean age at menarche, study vs. control: 16.4 ± 0.7 vs. 12.6 ± 0.9 years). To measure NPY and IGF-1 we used a radioimmunoassay method, whereas cortisol was measured with an enzyme immunoassay. Blood was collected between 08.00 and 09.00 following an overnight fast. NPY was higher in girls with CDP (181.6 ±106.4 pg/ml) than in girls with NP (55.5 ± 26.3 pg/ml; p < 0.001). In the former group, cortisol was higher (397.3 ± 241.6 nmol/l) than in NP girls (142.7 ±98.0 nmol/l; p < 0.01). Levels of IGF-I in CDP girls were lower than in NP girls (558.0 ± 122.6 vs. 756.5 ± 226.8 ng/ml; p < 0.01). The results corroborate the involvement of NPY in sexual maturation and its role in delayed puberty.

Neuropeptide Y inhibits 3[H]noradrenaline release in the rat vas deferens independently of cAMP levels

The purpose of the present investigation was to ascertain the functional significance of the reduction in cyclic AMP (cAMP) levels in the inhibitory action of neuropeptide Y (NPY) on [ 3H]noradrenaline ([ 3H]NA) release, as well as to further characterize the subtype(s) of NPY receptors involved in the peptide's actions in the rat vas deferens. We studied the effects of NPY, carboxyterminal fragments of this peptide and the NPY analog [Leu 31, Pro 34]-NPY on three functional responses, namely, the release of [ 3H]NA and the associated muscle contractions evoked by electrical stimulation, and the accumulation of cAMP stimulated by forskolin. NPY, a known inhibitor of the electrically-evoked [ 3H]NA release and neurogenic contractions is also a potent inhibitor of the forskolin-stimulated cAMP synthesis in the prostatic portion of the rat vas deferens. However, the ability of NPY to inhibit cAMP accumulation is lost upon tissue denervation, suggesting that this is likely to be a prejunctional effect. Elevation of cAMP levels by the use of the cell permeant analog of cAMP, 8-( p-chlorophenylthio)-cAMP (8pCTcAMP) increases the electrically-evoked release of [ 3H]NA. However, the inhibition of [ 3H]NA release by NPY is not prevented by 8pCPTcAMP. Structure-activity relationship studies reveal that NPY and related peptides inhibit the release of [ 3H]NA, the muscle contractions and the synthesis of cAMP with a similar pharmacological profile. NPY is the most potent inhibitory agent, whereas [Leu 31,Pro 34]-NPY and NPY 13–36, the respective Y 1 and Y 2 selective agonists, display similar potencies to inhibit the three responses. It is concluded that NPY inhibits neurotransmission in the rat vas deferens through the activation of a peptide receptor different from the known NPY-Y 1 or NPY-Y 2 receptor subtypes. NPY receptor activation in the vas deferens is negatively coupled to adenylyl cyclase activity. This intracellular signalling pathway is, however, not likely to mediate the peptide effects on the prejunctional regulation of noradrenaline release.

Neuropeptide Y inhibits adenylyl cyclase activity in rabbit retina.

Neuropeptide Y is known to be present in significant amounts in the retina of most vertebrates, but its physiological actions are largely unknown. We have therefore studied its effects on the intracellular cyclic AMP accumulation in rabbit retina. Neuropeptide Y had no effect on the basal cyclic AMP level but was found to inhibit the forskolin induced cyclic AMP accumulation. There were no differences between the effects of neuropeptide Y 1-36 and neuropeptide Y 13-36 (2.4 x 10(-6) M) suggesting the presence of the Y2 subtype of neuropeptide Y receptor. D-myo-inositol-1,2,6-trisphosphate, a novel neuropeptide Y-antagonist, reduced per se the forskolin induced cyclic AMP production. The pronounced inhibitory effect of neuropeptide Y on the forskolin induced cyclic AMP production was, on the other hand, totally abolished by D-myo-inositol-1,2,6-trisphosphate. The results indicate that neuropeptide Y acts on Y2 receptors in the retina to cause an inhibition of the adenylyl cyclase activity which could be antagonized by D-myo-inositol-1,2,6-trisphosphate. Such an inhibitory action of neuropeptide Y is similar to what has been found in brain tissue, but it has not previously been reported in the retina for neuropeptide Y or any of the other retinal neuropeptides.

Inhibitory action of neuropeptide Y on agonist-induced responses in isolated guinea pig trachea

The effect of neuropeptide Y (NPY) was tested on isolated guinea pig trachea. At 30 nM, NPY induced a weak but significant contractile response which was on average less than 6% of responses elicited by standard spasmogens. This myotropic action of NPY was blocked by indomethacin. In addition to its contractile activity, NPY greatly reduced the maximal response to vasoactive intestinal peptide (VIP), noradrenaline (NA), substance P (SP) and 5-hydroxytryptamine (5-HT), without affecting their pD 2 values. However, NPY did not influence the response induced by histamine and carbamylcholine. Pretreatment of reduce the action of NPY on NA-elicited relaxation. This latter effect was however blocked in the presence of tetrodotoxin. In conclusion, NPY inhibits responses elicited by various agonists in the guinea pig trachea. This effect seems to be mediated at both pre- and postjunctional levels. The postjunctionally mediated inhibitory action of NPY appears to be expressed especially with agents that generate prostaglandins concomitantly with inducing their response. In contrast, the NPY-evoked inhibition of NA-evoked relaxation seems to be mediated via a prejunctional mechanism.

Effect of synthetic porcine neuropeptide Y (NPY) on splanchnic blood flows and Exocrine pancreatic secretion in dogs

This study examined the effect of synthetic porcine neuropeptide Y on the splanchnic blood flows and the exocrine pancreatic secretion in dogs. Graded doses of neuropeptide Y (0.1-5 microg/kg, intravenous) caused dose-dependent reduction of the secretin-stimulated exocrine pancreatic secretion and of the blood flows in the superior mesenteric artery, the portal vein, and the pancreatic tissue. Neuropeptide Y at 5 microg/kg reduced the blood flows to 45.9 +/- 13.3% (superior mesenteric artery), 63.0 +/- 10.5% (portal vein), and 77.9 +/- 4.8% (pancreatic tissue), respectively. This dose also reduced secretin-stimulated pancreatic juice volume and CCK-8 plus secretin-stimulated protein output to 65.2 +/- 9.3 and 63.3 +/- 14.0%, respectively. This study shows a potent vasoconstrictor effect of neuropeptide Y on splanchnic vessels. Neuropeptide Y also inhibited exocrine pancreatic secretion in a significant correlation with the reduction in pancreatic tissue blood flow, which suggests that reduction in the blood flow may be one of the possible mechanisms of the inhibitory action of neuropeptide Y on exocrine secretion.