Atrial natriuretic factor: radioimmunoassay and effects on adrenal and pituitary glands

A simple and sensitive radioimmunoassay was developed for measurement of immunoreactive atrial natriuretic factor (IR-ANF) in rat and human plasma and in rat atria. The two atria contain about 20 micrograms ANF per rat. The right atrium contained 2.5 times more ANF than did the left. Ether anesthesia and morphine markedly increased IR-ANF in rat plasma. The concentration of IR-ANF in plasma of clinically normal human subjects was 65.3 +/- 2.5 pg/ml. Paroxysmal tachycardia and rapid atrial pacing significantly increased IR-ANF in human plasma. Two- to seven-fold higher concentrations were found in coronary sinus blood than in the peripheral circulation. In the plasma of rats and humans, circulating ANF is probably a small-molecular-weight peptide. ANF acts on the adrenal and the pituitary. ANF inhibits aldosterone secretion from rat zona glomerulosa and steroid secretion by bovine adrenal zona glomerulosa and fasciculata. ANF stimulated the basal secretion of arginine vasopressin (AVP) in vitro and inhibited KCl-stimulated release of AVP.     

Plasma immunoreactive atrial natriuretic factor (IR-ANF) increases markedly after alpha 2-adrenergic stimulation with clonidine in normally-hydrated rats

Clonidine, an alpha 2-adrenergic agonist, induced a marked, dose-related increase of plasma IR-ANF in normally-hydrated rats. Maximal ANF release was observed at 10 min after injection of 50 micrograms clonidine, rising from 40.5 +/- 4.6 pg/ml (X +/- SEM) to 1064.4 +/- 22.4 pg/ml. This effect on plasma IR-ANF was partially blocked by pretreatment with 0.8 mg naloxone, whereas synthetic Arg8-vasopressin (AVP) did not inhibit clonidine's action. These findings indicate that increased ANF release may be involved in the mechanism of clonidine-induced diuresis. The clonidine's effect on ANF release may be mediated via activation of opioid receptors besides stimulation of alpha 2-adrenergic receptors.     

Specific binding of atrial natriuretic factor to renal glomeruli in Doca- and Doca-salt-treated rats correlation with atrial and plasma levels

Since volume expansion and high blood pressure (BP) are known stimuli of atrial natriuretic factor (ANF) release, and since this peptide may be involved in mineralocorticoid escape, we investigated the effects of chronic deoxycorticosterone (DOCA) and DOCA-NaC1 treatment on renal glomerular ANF receptor density and affinity in relation to atrial and plasma ANF levels. An increase in plasma immunoreactive ANF (IR-ANF) was observed both after two and four weeks of treatment. IR-ANF concentrations were elevated in the left atrium only in four-week DOCA treated rats. Administration of the mineralocorticoid alone resulted in a decreased density of glomerular ANF receptors in both time periods investigated. DOCA-NaC1-treated animals presented an increased receptor density during the pre-hypertensive stage (2 weeks) and a reduced density in the later hypertensive period (4 weeks). Receptor affinity in both groups was identical to that in the controls after 2 weeks and was augmented after 4 weeks of treatment. Our data suggest that the down-regulation of renal glomerular ANF receptors during chronic DOCA-NaC1 administration may play a role in the maintenance of high BP in this model of volume-expanded hypertension.     

Immunoreactive atrial natriuretic factor (IR-ANF) in human plasma

A direct radioimmunoassay for ANF in human plasma was developed. A synthetic alpha-human atrial peptide (Ser 99-Tyr 126) was used for preparation of the iodinated tracer and the standards. The sensitivity of the method is 1.9 pg/ml. Concentration of immunoreactive ANF (IR-ANF) in plasma of 59 clinically normal subjects was 65.3 +/- 2.5 pg/ml (mean +/- SE). In two patients who underwent atrial pacing an increase of about 100 percent in circulating IR-ANF was observed. IR-ANF was extracted from human plasma by Vycor glass and purified by HPLC. The main immunoreactive isolated peak contained a low molecular weight peptide.     

Atrial natriuretic factor is a circulating hormone

The radioimmunoassay of atrial natriuretic factor (ANF) has been applied for determination of immunoreactive ANF (IR-ANF) in rat plasma. Immunoreactive ANF has been extracted from rat plasma by immunoaffinity column on Sepharose-4B anti-ANF or by Vycor glass. The mean concentrations of IR-ANF in ether anesthetized rats were found to be 1.61 +/- 0.14 ng/ml in female and 1.25 +/- 0.21 ng/ml in male rats when extracted on Sepharose-4B anti-ANF, and 1.21 +/- 0.10 ng/ml in females and 1.02 +/- 0.11 ng/ml in males when extracted by Vycor glass. A close linear correlation has been observed between the plasma IR-ANF concentrations in aorta and jugular vein. The described results indicate that atrial cardiocytes secrete atrial natriuretic factor into plasma. The heart is, therefore, an endocrine organ.     

Neuropeptide Y (NPY)-induced feeding behavior in female rats: comparison with human NPY ([Met17]NPY), NPY analog ([norLeu4]NPY) and peptide YY

Porcine neuropeptide Y (pNPY) administered into the third ventricle of the brain is known to elicit a powerful feeding response in steroid-treated ovariectomized and intact male rats. The present study compared the effects of pNPY and 3 structurally related peptides, human NPY (hNPY), an analog of NPY (NPY-A, [norLeu4]NPY) and peptide YY (PYY) on feeding behavior in intact female rats. Intraventricular administration of pNPY, hNPY, NPY-A and PYY over a dose range of 0.5 to 10 micrograms evoked feeding behavior to a varying extent. Cumulative food intake during 60 and 120 min was increased in a dose-related fashion at 0.5 and 2.0 microgram for the 4 peptides. Whereas the 10-micrograms dose of pNPY evoked a feeding response smaller than that seen after 2 micrograms, the responses to either 10 micrograms hNPY or 10 micrograms PYY were similar to that seen after 2 micrograms. The effects of these peptides on the time spent eating were quite different: while pNPY increased the time spent eating, this effect was not dose-related, whereas hNPY, NPY-A and PYY produced dose-related increments in the time spent eating. The most dramatic increment in local eating rate was observed after 2.0 micrograms pNPY, with lesser increments seen after 2.0 microgram hNPY and NPY-A. This increased local eating was apparently responsible for the highest cumulative food intake observed. These results demonstrate that (a) 2 micrograms pNPY is equally effective in stimulating feeding behavior in intact female rats as it is in steroid-primed ovariectomized female and intact male rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal and peripheral modulation of gastric acid secretion and arterial pressure by neuropeptide Y, peptide YY, and pancreatic polypeptide in rats

Spinal and peripheral modulation of pentagastrin-stimulated gastric acid secretion by the pancreatic polypeptide-fold (PP-fold) peptides, neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP), in urethane-anesthetized rats was evaluated. Neuropeptide Y, PYY, and PP (400 pmol) were administered via intravenous (IV) and intrathecal (IT) injections. The ₂ antagonist, yohimbine, was used to evaluate the role of the ₂ adrenergic receptors in the modulation of pentagastrin-stimulated gastric acid secretion by NPY, PYY, and PP. Peptide YY and PP (IV) rapidly increased pentagastrin-stimulated gastric acid secretion. Peptide YY and PP (IT) increased pentagastrin-stimulated gastric acid secretion following administration into the thoracic (T8–T10) region of the spinal cord. The ₂ adrenergic receptor antagonist, yohimbine, did not modify the increases in pentagastrin-stimulated gastric acid secretion following PYY and PP (IV or IT) administration. Neuropeptide Y (IT) decreased pentagastrin-stimulated gastric acid secretion. However, in the presence of ₂ adrenergic receptor blockade, pentagastrin-stimulated gastric acid secretion was potentiated by NPY (IT) administration. Therefore, the inhibitory effect of NPY (IT) on pentagastrin-stimulated gastric acid secretion required the activation of ₂ adrenergic receptors in the spinal cord of rats. Mean arterial blood pressure (MAP) was increased immediately following NPY and PYY (IV) administration. During the same time period, PP (IV) decreased MAP in anesthetized rats. Mean arterial blood pressure was rapidly increased by NPY and PYY (IT) in anesthetized rats. The increase in MAP following PYY (IT) was partially attenuated in the presence of yohimbine. The modulation of MAP and gastric acid secretion by the PP-fold peptides occurred by independent mechanisms at spinal and peripheral sites in the rat. The modulation of pentagastrin-stimulated gastric acid secretion by PYY and PP in rats differed from that of the third member of the PP-fold family, NPY, following spinal and peripheral administration.     

Effects of pinealectomy and exogenous melatonin on ghrelin and peptide YY in gastrointestinal system and neuropeptide Y in hypothalamic arcuate nucleus: immunohistochemical studies in male rats

It is reported that the pineal gland and its main hormone melatonin may have a role in the regulation of ghrelin synthesis in the brain. Stomach is the place where ghrelin is predominantly expressed and secreted. One aim of this study was to investigate possible effects of pinealectomy and melatonin treatment on gastric ghrelin amount. The studies on the effects of the pineal gland on leptin and ghrelin arises the question whether the pineal gland has also effects on the other energy-regulatory peptides such as peptide YY (PYY) and neuropeptide Y (NPY). Therefore, we also aimed to investigate the changes in the immunohistochemical staining of intestinal PYY and hypothalamic NPY following pinealectomy and melatonin treatment. Serum PYY levels were also investigated. Sprague-Dawley rats were divided into four groups as sham-operated (SHAM), sham-operated with melatonin treatment (SHAM-MT), pinealectomised (PNX) and melatonin-treated PNX (PNX-MT) groups. The cells immunostained for ghrelin were abundant throughout the gastric mucosa in all the groups. Neither pinealectomy nor exogenous melatonin affected significantly immunohistochemical staining of ghrelin in stomach. Pinealectomy resulted in a significant increase in immunohistochemical staining of PYY in ileum. The results of serum PYY measurement corresponded closely to the data obtained by immunohistochemical analysis of PYY in ileum, being significantly lower and higher in SHAM and PNX groups, respectively. Pinealectomy caused a decrease in NPY synthesis in ARC as understood from low immunohistochemical staining of NPY. Melatonin treatment increased NPY synthesis in SHAM rats and restored reduction in NPY synthesis caused by pinealectomy. In conclusion, the pineal gland and its main hormone melatonin can be suggested to have a role in the regulation of NPY synthesis in ARC and PYY in gastrointestinal system.     

Effects of peptide YY(3-36) on PRL secretion: pituitary and extra-pituitary actions in the rat

Polypeptide YY(3-36) (PYY(3-36)) is a gastrointestinal secreted molecule, agonist of neuropeptide Y (NPY) receptor subtypes Y2 and Y5, that has been recently involved as anorexigenic signal in the network controlling food intake. Notably, several factors primarily involved in food intake control and energy homeostasis (as leptin, orexins, ghrelin and NPY) have been linked also to the regulation of anterior pituitary hormone secretion and carry out pleiotropic effects upon the reproductive axis. However, whether similar actions are conducted by PYY(3-36) remains so far largely unexplored. Present studies were undertaken to analyze the potential effects of PYY(3-36) in the control of prolactin (PRL) secretion in the rat. To this end, responses to PYY(3-36) in terms of PRL secretion were monitored in vitro, after pituitary exposure to 10(-8) to 10(-6) M concentrations, and in vivo, after i.p. administration of different doses of PYY(3-36) (3, 10 and 30 microg/kg) to prepubertal male and female rats. In addition, the in vivo effects of PYY(3-36) were tested after central (i.c.v.) administration of 3 nmol of the peptide to prepubertal rats, and in hyperprolactinaemic aged females. PYY(3-36) stimulated, in a dose-dependent manner, in vitro PRL secretion by pituitaries from prepubertal male and female rats. In contrast, systemic administration of PYY(3-36) failed to modify serum PRL levels, whereas central infusion of PYY(3-36) significantly inhibited PRL secretion in prepubertal rats. Finally, PRL secretion was stimulated in aged hyperprolactinaemic female rats by systemic administration of PYY(3-36). In conclusion, the anorexigenic peptide PYY(3-36) may participate in the control of PRL secretion in the prepubertal rat, acting at pituitary (stimulatory effect) and extra-pituitary (likely inhibitory action at the hypothalamus) sites of the lactotrope axis. Moreover, net actions of PYY(3-36) on PRL secretion may depend on the age and prevailing PRL levels.     

Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens

In the present experiments the gut hormone peptide YY3-36 (PYY3-36), which inhibits neuropeptide Y (NPY) release, was used as a tool to study the cardiovascular effects of endogenous NPY under different dietary regimens in rats instrumented with a telemetry transmitter. In a first experiment, rats were placed on a standard chow diet ad libitum and in a second experiment on a high-fat diet ad libitum. After 6 wk, PYY3-36 (300 microg/kg) or vehicle was injected intraperitoneally. In a third experiment, PYY3-36 or vehicle was administered after 14 days of 50% restriction of a standard chow diet. In food-restricted rats, PYY3-36 increased mean arterial pressure (7 +/- 1 mmHg, mean +/- SE, P < 0.001 vs. saline, 1-way repeated-measures ANOVA with Bonferroni t-test) and heart rate (22 +/- 4 beats/min, P < 0.001) during 3 h after administration. Conversely, PYY3-36 did not influence mean arterial pressure (0 +/- 1 mmHg) and heart rate (-8 +/- 5 beats/min) significantly in rats on a high-fat diet. Rats fed standard chow diet ad libitum showed an intermediate response (mean arterial pressure 4 +/- 1 mmHg, P < 0.05, and heart rate 5 +/- 2 beats/min, not significant). Thus, in our studies, divergent cardiovascular responses to PYY3-36 were observed in rats on different dietary regimens. These findings suggest that the cardiovascular effects of PYY3-36 depend on the hypothalamic NPY release, which is increased after chronic food restriction and decreased during a high-fat diet.     

Molecular evolution of the neuropeptide Y (NPY) family of peptides: cloning of three NPY-related peptides from the sea bass (Dicentrarchus labrax)

Neuropeptide Y (NPY) is a 36-amino-acid peptide that is widely and abundantly expressed in the central nervous system of all vertebrates investigated. Related peptides have been found in various vertebrate groups: peptide YY (PYY) is present in gut endocrine cells of many species and pancreatic polypeptide (PP) is made in the pancreas of all tetrapods. In addition, a fish pancreatic peptide called PY has been reported in three species of fishes. The evolutionary relationships of fish PY have been unclear and it has been proposed to be the orthologue (species homologue) of each of the three tetrapod peptides. We demonstrate here with molecular cloning techniques that the sea bass (Dicentrarchus labrax), an acanthomorph fish, has orthologues of both NPY and PYY as well as a separate PY peptide. Sequence comparisons suggest that PY arose as a copy of the PYY gene, presumably in a duplication event separate from the one that generated PP from PYY in tetrapods. PY sequences from four species of fish indicate that, similar to PP, PY evolves much more rapidly than NPY and PYY. The physiological role of PY is unknown, but we demonstrate here that sea bass PY, like NPY and PYY but in contrast to the tetrapod PP, is expressed in brain.     

Co-localization of peptides in the Brockmann bodies of the cod (Gadus morhua) and the rainbow trout (Oncorhynchus mykiss)

Endocrine cells exhibiting immunoreactivity to FMRFamide-like, LPLRFamide-like, neuropeptide Y(NPY)-like and peptide YY(PYY)-like peptides were found in the periphery of the Brockmann bodies of the cod, Gadus morhua, and rainbow trout, Oncorhynchus mykiss. No immunoreactivity or very weak labelling was found with antisera to pancreatic polypeptide (PP). Vasoactive intestinal polypeptide (VIP)-like immunoreactivity was found in nerve fibres, whereas labelling with VIP antiserum in endocrine cells disappeared after preincubation with nonimmune serum. There were always more immunoreactive cells in the rainbow trout than in the cod. No immunoreactivity could be seen with antisera to gastrin/cholecystokinin (CCK) or enkephalin. Double-labelling studies were performed to study the colocalization of the peptides in peripheral endocrine cells. Cells immunoreactive to NPY were also labelled with antisera to FMRFamide, LPLRFamide and PYY. The co-localization pattern of NPY varied; in some Brockmann bodies, a population of the immunoreactive cells showed co-localization and others contained NPY-like immunoreactivity only, whereas in other Brockmann bodies, all NPY-labelled cells also contained FMRFamide-like, LPLRFamide-like and PYY-like immunoreactivity. Cells immunoreactive to PYY similarly contained FMRFamide-like, LPLRFamide-like and NPY-like immunoreactivity, comparable to the patterns observed with NPY. Glucagon-like immunoreactivity was found at the periphery of the Brockmann bodies. A subpopulation of the glucagon-containing cells contained NPY-like immunoreactivity. PYY-like immunoreactivity was also found co-localized with glucagon-like immunoreactivity, as were FMRFamide-like and LPLRFamide-like immunoreactivity. Therefore, either NPY-like and PYY-like immunoreactivity together with FMRFamide-like and LPLRFamide-like immunoreactivity occur in the same endocrine cells of the Brockmann body of the cod and rainbow trout, or a hybrid NPY/PYY-like peptide recognized by both NPY and PYY antisera is present in the Brockmann body.     

Robust feeding following central administration of neuropeptide Y or peptide YY in chicks, Gallus domesticus

Neuropeptide Y (NPY) and peptide YY (PYY) were injected intracerebroventricularly (ICV) in broiler chicks. Both NPY and PYY markedly increased food intake during the first hour post-injection compared to saline (SAL) controls. Food intake doubled in chicks given 5 micrograms NPY. A response surface analysis suggested that following ICV injection of NPY, maximum food intake occurred, using a dose of 9 micrograms. In contrast, an estimated dose between one and 5 micrograms PYY resulted in maximum food intake, giving the latter a slightly higher potency. Time spent drinking was not significantly different among NPY, PYY and SAL groups. Chicks given NPY or PYY also spent significantly less time standing while those given PYY spent significantly less time preening compared to controls.     

Neuropeptide Y (NPY) and peptide YY (PYY) receptors in rat brain

1. Specific binding sites for neuropeptide Y (NPY) and peptide YY (PYY) were investigated in rat brain areas using quantitative receptor autoradiography with 125I-Bolton-Hunter NPY (125I-BH-NPY) and 125I-PYY, radioligands for PP-fold family peptides receptors. 2. There were no differences between localization of 125I-BH-NPY and 125I-PYY binding sites in the rat brain. High densities of the binding sites were present in the anterior olfactory nucleus, lateral septal nucleus, stratum radiatum of the hippocampus, posteromedial cortical amygdaloid nucleus, and area postrema. 3. In cold ligand-saturation experiments done in the presence of increasing concentrations of unlabeled NPY and PYY, 125I-BH-NPY and 125I-PYY binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, molecular layer of the cerebellum, and area postrema was single and of a high affinity. There was a significant difference between the affinities of 125I-BH-NPY (Kd = 0.96 nM) and 125I-PYY binding (Kd = 0.05 nM) to the molecular layer of the cerebellum. The binding of the two radioligands to the other areas examined had the same affinities. 4. When comparing the potency of unlabeled rat pancreatic polypeptide (rPP), a family peptide of NPY and PYY, to inhibit the binding to the areas examined, rPP displaced 125I-BH-NPY and 125I-PYY binding to the area postrema more potently than it did the binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, and molecular layer of the cerebellum. 5. Thus, the quantitative receptor autoradiographic method with 125I-BH-NPY and 125I-PYY revealed differences in binding characteristics of specific NPY and PYY binding sites in different areas of the rat brain. The results provide further evidence for the existence of multiple NPY-PYY receptors in the central nervous system.     

Peptide YY and neuropeptide Y induce villin expression, reduce adhesion, and enhance migration in small intestinal cells through the regulation of CD63, matrix metalloproteinase-3, and Cdc42 activity

Peptide YY (PYY) and neuropeptide Y (NPY) are regulatory peptides synthesized in the intestine and brain, respectively, that modify physiological functions affecting nutrient assimilation and feeding behavior. Because PYY and NPY also alter the expression of intestine-specific differentiation marker proteins and the tetraspanin CD63, which is involved in cell adhesion, we investigated whether intestinal cell differentiation could be linked to mucosal cell adhesion and migration through these peptides. PYY and NPY significantly decreased cell adhesion and increased cell migration in a dose-dependent manner prior to cell confluency in our model system, non-tumorigenic small intestinal hBRIE 380i cells. Both peptides reduced CD63 expression and CD63-dependent cell adhesion. CD63 overexpression increased and antisense CD63 cDNA decreased intestinal cell adhesion. In parallel, both PYY and NPY increased expression of matrix metalloproteinase-3 (MMP-3) to a level sufficient to induce cell migration by activating the Rho GTPase Cdc42. The effects of both peptides on cell migration were blocked in cells constitutively overexpressing dominant-negative Cdc42. PYY and NPY also significantly induced the expression of the differentiation marker villin, which could be eliminated by an MMP inhibitor at a concentration that inhibits cell migration. Increased MMP-3 activity, which enhanced cell migration, also induced villin mRNA levels. Therefore, these data indicate that the alteration of adhesion and migration by PYY and NPY occurs in part by synchronous modulation of three proteins that are involved in extracellular matrix-basolateral membrane interactions, CD63, MMP-3 and Cdc42, and that PYY/NPY regulation of expression of mucosal proteins such as villin is linked to the process of cell migration and adhesion.     

Effects of neuropeptide Y (NPY) at the sympathetic neuroeffector junction. Can pre- and postjunctional receptors be distinguished?

Neuropeptide Y (NPY) is widely distributed in central and peripheral neurons. In sympathetic postganglionic neurons, NPY coexists with noradrenaline. NPY and its structural relative peptide YY (PYY) appear to exert three principally different effects at the sympathetic neuroeffector junction. Firstly, NPY has a direct postjunctional effect; this effect is manifested as a vasoconstriction when studied on the guinea pig iliac vein. Secondly, NPY has an indirect postjunctional effect in that it potentiates the response to various vasoconstrictors; this was studied on the rabbit femoral artery and vein, using noradrenaline and histamine, respectively, as vasoconstrictors. Thirdly, NPY acts prejunctionally in that it suppresses the release of noradrenaline from sympathetic nerve terminals; this was studied in the rat vas deferens. The aim of the investigation was to examine whether the three effects of NPY were mediated by the same type of receptor. For this purpose, we examined the effects of a series of NPY-related peptides, namely NPY, PYY, desamido-NPY, and five C-terminal fragments (NPY 19-36, NPY 24-36, PYY 13-36, PYY 24-36 and PYY 27-36). NPY and PYY were active in all three assay systems. The C-terminal amide appears to be crucial for maintaining the biological activity, since desamido-NPY was inactive in the three test systems. Interestingly, PYY 13-36 was almost as active as NPY and PYY in suppressing the electrically evoked contractions of the vas deferens; PYY 13-36 was inactive in the two other test systems. None of the shorter fragments had any biological activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides

The effects of neuropeptide Y (NPY), peptide YY (PYY), desamido-NPY and five C-terminal fragments of NPY or PYY were tested on different smooth muscle preparations in vitro. The fragments were NPY 19-36, NPY 24-36, PYY 13-36, PYY 24-36 and PYY 27-36. NPY and PYY appear to exert three principally different effects at the level of the sympathetic neuroeffector junction. Firstly, they have a direct post-junctional effect, leading to constriction of certain blood vessels; this was studied on the guinea-pig iliac vein. Secondly, they potentiate the response to various vasoconstrictors; this was studied on the rabbit femoral artery and vein, using noradrenaline and histamine, respectively, as agonists. Thirdly, NPY and PYY act prejunctionally in that they suppress the release of noradrenaline from sympathetic nerve endings upon stimulation; this was studied in the rat vas deferens. NPY and PYY were approximately equipotent in constricting the guinea-pig iliac vein, while desamido-NPY and the fragments were without effect. Desamido-NPY and the fragments were ineffective also in potentiating the response to noradrenaline in the rabbit femoral artery, nor did they potentiate the response to histamine in the rabbit femoral vein. NPY and PYY potentiated the response to noradrenaline in the artery, as well as the response to histamine in the vein. The NPY- and PYY-induced suppression of noradrenaline release from the prostatic portion of the rat vas deferens was reproduced by PYY 13-36 but not by the shorter fragments nor by desamido-NPY. In conclusion, a C-terminal portion seems to be sufficient for exerting the prejunctional effect of NPY and PYY, while the whole sequence seems to be required for post-junctional (direct and modulatory) effects. An amidated C-terminal is crucial for maintaining the biological activity of NPY. Desamido-NPY and the fragments that were inactive as agonists also seemed inactive as antagonists.     

Feeding after fourth ventricular administration of neuropeptide Y receptor agonists in rats

Neuropeptide Y (NPY) and peptide YY (PYY) stimulate food intake after injection into the fourth cerebral ventricle, suggesting that NPY receptors in the hindbrain are targets for the stimulatory effect of these peptides on food intake. However, the NPY/PYY receptor subtype mediating the feeding response in the hindbrain is not known. To approach to this question we compared dose-effect of several NPY receptor agonists to stimulate food intake in freely-feeding rats 60- and 120-min after injection into the fourth cerebral ventricle. At the 120-min time point, PYY was 2- to 10-times as potent as NPY over the dose-response range and stimulated twice the total intake at the maximally effective dose (2-fold greater efficacy). NPY was 2-times as potent as the Y1, Y5 receptor agonist, [Leu(31)Pro(34)]NPY but acted with comparable efficacy. The Y5-, Y2-differentiating receptor agonist, NPY 2-36, was comparable in potency to PYY at low doses but equal in efficacy NPY and [Leu(31)Pro(34)]NPY. The Y2 receptor agonist, NPY 13-36, produced only a marginal effect on total food intake. The profile of agonist potency after fourth cerebral ventricle administration is similar to the profile obtained when these or related agonists are injected in the region of the hypothalamus. Agonists at both Y1 and Y5 receptors stimulated food intake with a rank order of potency that does not conclusively favor the exclusive involvement of a single known NPY receptor subtype. Thus it is possible that the ingestive effects of NPY and PYY are mediated by multiple or novel receptor subtypes in the hindbrain. And the relatively greater potency and efficacy of PYY raises the possibility that a novel PYY-preferring receptor in the hindbrain is involved in the stimulation of food intake.     

Plasma and atrial content of atrial natriuretic factor in cardiomyopathic hamsters

Immunoreactive atrial natriuretic factor (IR-ANF) was measured in plasma and atrial extracts from normal and cardiomyopathic Syrian golden hamsters. Plasma IR-ANF was increased from 84.8 ± 9.8 pg/ml(n = 17) to 234 ± 23 (n = 25; P<.0001) in hamsters with moderate failure, and to 1085 ± 321 pg/ml (n = 10; P<.02) in animals with severe failure. Plasma IR-ANF increased with increased atrial hypertrophy. Atrial IR-ANF content was essentially the same in normal animals and in those with moderate heart failure (3.06 ± 0.28 vs 3.17 ± 0.19 μg/100 g body wt., P<.001) and lower in the majority of those with severe failure (1.82 μg/100 g body wt., P<.001). The elevations of IR-ANF in plasma are similar to those seen in patients with congestive heart failure. Our studies do not support bioassay results showing a deficiency of atrial ANF content as being important in the congestive heart failure associated with cardiomyopathy in the hamster.