Effect of central administration of prolactin-releasing peptide on feeding in chicks

Prolactin-releasing peptide (PrRP) is one of the inhibitory factors in feeding regulation of mammals. However, no information is available for avian species. The present study was done to clarify the effect of intracerebroventricular (ICV) injection of PrRP on feeding in chicks. Firstly, we found that ICV injection of PrRP (94–1500 pmol) significantly increased food intake in chicks. The result was completely different from those obtained in mammals. The orexigenic effect of PrRP was significantly weaker than that of neuropeptide Y (NPY), a potent orexigenic peptide, on an equimolar basis. The orexigenic effect of NPY was further enhanced with coinjection of PrRP. These results suggest the existence of a novel orexigenic mechanism in the chick brain, which might differ from NPY-involved feeding regulatory pathway. In addition, ICV injection of PrRP significantly decreased the rectal temperature, but the effect was weaker than that of NPY, suggesting that PrRP may inhibit energy expenditure in chicks. Taken together, we showed here that PrRP may be involved in the regulation of both feeding behavior and energy metabolism in the chick brain.     

Central administration of prolactin-releasing peptide stimulates oxytocin release in rats

The localization of nitric oxide synthase (NOS) was investigated by immunocytochemistry and immunoblotting using an antiserum against neuronal NOS in the rat, mouse, guinea pig, rabbit and cat retinae. Western blot analysis of retinal tissue extracts showed that the NOS-immunoreactive band of 155 kDa was present in all species. In the rat, mouse, guinea pig and rabbit retinae, two types of amacrine cells and a class of displaced amacrine cells were consistently NOS-labeled. In the cat retina, unlike other mammals, one type of amacrine cells and two types of displaced amacrine cells showed NOS immunoreactivity. NOS immunoreactivity was further found in some bipolar cells of the rat and guinea pig, some interplexiform cells of the mouse, some photoreceptor cells of the rabbit and some Müller cells of the cat.     

Stimulation of gastric acid secretion by dimaprit in unanesthetized rats

In unanesthetized rats, dimaprit and histamine given by intravenous infusion were about equipotent in stimulating gastric acid secretion. The maximal rate of acid secretion in response to dimaprit was significantly greater than to histamine but not significantly different from the response to pentagastrin.     

Stimulation of insulin and glucagon secretion by vasoactive intestinal peptide.

In vivo, vasoactive intestinal peptide (VIP) produces simultaneous increases in blood glucose and insulin levels. In order to determine whether VIP, like its homologues, also stimulates insulin secretion directly, studies were made in controlled glucose media employing the vascularly perfused cat pancreas. VIP stimulated insulin secretion significantly in the presence of constant physiological concentrations of glucose. The highest insulin response to VIP (100.3+/-8.1 muU/min) approached the highest insulin response to glucose (119.9 +/- 12.0 muU/min). In the absence of glucose, the insulin response to VIP was insignificant. Unexpectedly, VIP was found to be a more effective stimulant of glucagon than of insulin secretion. The highest glucagon response to VIP (327+/-51% of control levels) was attained in the presence of physiological concentrations of glucose and equalled the glucagon response obtained upon withdrawal of glucose from the perfusate. The glucagon response to VIP was blocked by increasing the glucose in the perfusate. These studies indicate the VIP present in pancreatic islets might play a role in the local control of pancreatic endocrine function.     

Intracerebroventricular administration of corticotropin-releasing factor antagonist attenuates arousal response accompanied by yawning behavior in rats

We have reported that an arousal response accompanied by yawning behavior can be evoked by electrical and chemical stimulation of the hypothalamic paraventricular nucleus (PVN) in rats, although the mechanism responsible for the arousal response accompanied by yawning evoked by PVN stimulation is still unknown. In the present study, we examined the involvement of corticotropin-releasing factor (CRF) in the arousal response during yawning induced by electrical stimulation of the PVN in anesthetized, spontaneous breathing rats using intracerebroventricular (icv) injection of alpha-helical CRF, a CRF antagonist (4.2 microg, lateral ventricle). The electrocorticogram (ECoG) was recorded to evaluate arousal responses during yawning. Fast Fourier transform was used to obtain the power spectrum in delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-20 Hz) bands. We also recorded the intercostal electromyogram as an index of inspiratory activity and blood pressure (BP) as an index of autonomic function to evaluate yawning response. PVN stimulation induced significant increases in relative powers of theta, alpha, and beta bands, but not delta band, concurrent with yawning events regardless of icv injection, though the relative powers after icv injection of alpha-helical CRF were significantly lower than those after saline injection. These findings suggest that CRF neurons in the PVN are primarily responsible for the arousal response accompanied by yawning behavior.     

Inhibitory effect of central calcitonin-gene related peptide (CGRP) on pancreatic secretion in conscious rats

The inhibitory effect of central administration of calcitonin-gene related peptide (CGRP) on pancreatic secretion stimulated by bile-pancreatic juice diversion was determined in conscious rats. Rats were prepared with separate cannulae for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. In addition, another cannula was stereotactically implanted into the left lateral cerebral ventricle. Rats were placed in restraint cages and experiments were conducted 4 d after the operation without anesthesia. An injection of CGRP (1 nmol/10 microl) into the left lateral cerebral ventricle (i.c.v.) inhibited pancreatic secretion as well as cholecystokinin (CCK) release induced by bile-pancreatic juice diversion. Intravenous infusion of alpha- and beta-adrenergic receptor antagonist, phentolamine and propranolol did not reverse the inhibition of pancreatic secretion. Intravenous infusion of CGRP did not affect pancreatic secretion or plasma CCK concentrations. The inhibitory action of central CGRP (i. c.v.) on pancreatic secretion and CCK release stimulated by bile-pancreatic juice diversion is partially mediated by an alpha-adrenergic mechanism, although its precise mechanism has not been elucidated.     

Involvement of central histamine receptors in corticosterone secretion induced by intraventricular administration of morphine

The effect of intracerebroventricular (i.c.v.) administration of morphine on corticosterone secretion was studied in conscious, unstressed rats. A dose-dependent increase in serum corticosterone levels was observed 1 h after morphine injection. The corticosterone response to morphine was antagonized in a dose-dependent manner, and at larger dose almost abolished, by i.c.v. pretreatment of rats with naloxone, an opioid receptor antagonist. Intraventricular pretreatment of rats with mepyramine and cimetidine, the histamine H₁- and H₂-receptor antagonists, significantly diminshed the corticosterone response to morphine.These results suggest that central opioid receptors are involved in the stimulating effect of morphine on the hypothalamo-pituitary-adrenocortical axis. Central histamine H₁- and H₂-receptors seem to be substantially involved in the stimulatory effect of morphine on corticosterone secretion in conscious, unstressed rats.The study was supported by the Polish Academy of Sciences, grant No 06.03.     

Antinociception induced in rats by intrathecal administration of antiserum against calcitonin gene-related peptide

To determine whether or not endogenous calcitonin gene-related peptide (CGRP) participates in pain transmission in the spinal dorsal horn, effects of an intrathecal injection of anti-CGRP antiserum on nociceptive threshold in the paw-pressure test was examined in non-arthritic and adjuvant arthritic rats. An intrathecal injection of the antiserum increased the nociceptive threshold in non-arthritic animals, while 0.9% saline, pre-immune serum and antiserum, previously absorbed by synthetic CGRP, were without effect. Adjuvant arthritic rats showed a hyperalgesia, and improvement occurred with intrathecal injection of the antiserum. Saline and absorbed antiserum were without effect on the hyperalgesia. These results suggest that the endogenous CGRP present in primary afferents probably has a facilitating function in nociceptive transmission in the spinal dorsal horn.     

中枢CRH在大鼠应激性体温升高和LPS性发热机制中的作用

目的:进一步观察中枢促肾上腺皮质激素释放激素(CRH)在大鼠应激性体温升高和脂多糖(LPS)性发热中枢机制中的作用。方法:第三脑室微量注射CRH受体拮抗剂α-helicalCRH(9-41)和LPS,测定大鼠结肠温度及脑腹中隔区精氨酸加压素(AVP)含量。结果:生理盐水对照组大鼠体温明显升高,最大升幅为(0.88±0.31)℃。第三脑室注射CRH受体拮抗剂α-helicalCRH(9-41)10min后再注射生理盐水组,90min内大鼠结肠温度未见明显波动,90min后体温开始上升,1.5h体温反应指数(TRI_1.5)明显低于生理盐水对照组,而脑腹中隔区AVP含量和TRI_3.5与对照组比较均没有明显差别。第三脑室注射300ng的LPS引起大鼠结肠温度双相性升高,其TRI_3.5明显高于生理盐水对照组。事先向第三脑室注射α-helicalCRH(9-41)(5μg)再注射LPS组,TRI_3.5明显高于LPS组,而脑腹中隔区AVP含量明显低于LPS组。结论:CRH介导应激诱导的早期体温升高。CRH可能通过诱导脑腹中隔区AVP的生成限制大鼠LPS性发热。在大鼠LPS性发热中,CRH可能是一种双相作用分子,一方面本身介导发热体温升高,另一方面又诱生发热体温负调节介质而限制发热体温的升高。     

Alternative role for prolactin-releasing peptide in the regulation of food intake

Prolactin-releasing peptide (PrRP) is a peptide ligand for the human orphan G-protein-coupled receptor hGR3/GPR10 and causes the secretion of prolactin from anterior pituitary cells. However, the lack of immunoreactive staining for PrRP in the external layer of the median eminence seems to rule out this peptide as a classical hypophysiotropic hormone and, furthermore, PrRP is less effective than another inducer of prolactin secretion, thyrotropin-releasing hormone, both in vitro and in vivo. Here we show a reduction in the expression of PrRP mRNA during lactation and fasting and an acute effect of PrRP on food intake and body weight, supporting the hypothesis of an alternative role for the peptide.     

Expression of prolactin-releasing peptide and its receptor in the human decidua

Human decidua and decidualized endometrial cells produce prolactin (PRL). Several growth factors and cytokines have been shown to regulate decidual PRL release, but a specific PRL-releasing substance remains to be characterized. Prolactin-releasing peptide (PrRP) is a peptide isolated from the brain and distinguished by its potent and specific stimulation of PRL release by cultured pituitary cells. Here, we demonstrate that human decidua expresses immunoreactive PrRP as well as the mRNAs encoding PrRP and its receptor. First trimester deciduas were obtained from women undergoing elective termination of pregnancy. Tissue specimens were stained by immunohistochemistry using a rabbit anti-human PrRP-31 antibody, and PrRP was localized in both epithelial cells of the decidual glands and in stromal cells, with diffuse distribution and no special relation with the neighbourhood of blood vessels. In primary cultures of decidual stromal cells, PrRP and PrRP receptor gene expression were detected using RT-PCR, and the identity of the PCR products was further confirmed by restriction enzyme digestion. The effect of PrRP on decidual PRL release was also evaluated, and there was a significant increase in PRL production (135 +/- 4% of control levels, P < 0.05) after incubation of decidual stromal cells with synthetic PrRP. The expression of PrRP and PrRP receptor in human decidual cells and the ability of PrRP to induce PRL secretion by cultured decidual cells suggests that this peptide may be a novel local modulator of decidual PRL release.     

Cellular localization of prolactin-releasing peptide messenger RNA in the rat brain.

Prolactin-releasing peptide (PrRP), a novel peptide identified as the endogenous ligand for an orphan receptor isolated from the pituitary, is a potent stimulator of prolactin release. To get a clue of the functional roles of the peptide, we performed in situ hybridization histochemistry for PrRP mRNA to define the cellular localization of PrRP-producing cells in the brain of the cycling adult female rat during diestrus. The PrRP mRNA-containing cells were located in the caudal part of the dorsomedial nucleus of the hypothalamus. In the brainstem, the cells were found in the caudal part of the solitary tract nucleus and in the caudal ventrolateral medulla (ventrolateral intermediate reticular field). Specific signals for PrRP mRNA were not detected in other brain regions. Although PrRP is a candidate for being a hypophysiotropic specific releasing factor, the discrete distribution of PrRP in the extrahypothalamic area suggests that the peptide has other physiological functions in the central nervous system.     

Increased thyroxine secretion following administration of dinitrophenol to rats

1. Feeding male rats 0.2% dinitrophenol (DNP) in the diet caused weight loss, a significant fall in the plasma protein bound iodine concentration, and a rise in the thyroxine secretion rate. Thyroxine concentration was raised in the liver and intestinal tract with contents, reduced in the carcass, and unchanged in the pelt.2. Radio-iodine uptake by the thyroid gland was unchanged but there was a significant fall in the thyroid/serum activity ratio.3. Five hours after tracer radiothyroxine, DNP treated rats had a reduced fraction of dose in the plasma, with raised concentrations in the liver and intestines.4. Fractional turnover rates of radiothyroxine in plasma, liver and carcass were raised in DNP treated animals.5. DNP caused a significant increase in the biliary clearance of radiothyroxine, when measured immediately after administration of tracer and 4 hr later.6. It is postulated that DNP displaces thyroxine from its plasma binding proteins and that the displaced hormone is excreted in the bile. This wastage together with increased demand resulting from DNP induced hypermetabolism results in increased output of thyroxine by the thyroid gland.     

Naloxone antagonizes a central histaminergic stimulation of corticosterone secretion in rats

The interaction of central opioid receptors with histaminergic stimulation of the hypothalamo-pituitary-adrenocortical axis, evaluated indirectly through corticosterone secretion, was investigated in conscious unstressed rats. To avoid any possible direct action on the adrenal cortex, all drugs were given intracerebroventricularly (i.c.v.). Histamine, 2-pyridylethylamine (PEA), a histamine H₁-receptor agonist, and 4-methyl-histamine (MeHA) and dimaprit, the H₂-receptor agonists, considerably increased the serum corticosterone levels 1 h after adminstration. Naloxone, an opioid receptor antagonist, almost abolished the corticosterone response to PEA and considerably reduced the responses to MeHA, dimaprit and histamine. The maximum inhibitory effects of naloxone on corticosterone responses induced by histamine and histamine agonists were comparable with those of the H₁-and H₂-receptor antagonists, mepyramine and cimetidine.These results strongly suggest that a major part of the histaminergic stimulation of the hypothalamopituitary-adrenal axis is mediated by central opioid receptorsThe study was supported by the Polish Academy of Sciences, grant No 06.03.     

Stimulation of histamine release by the peptide kinetensin

The peptide kinetensin isolated from pepsin-treated human plasma induced a dose-dependent release of histamine when exposed to rat peritoneal mast cells. The threshold concentration was around 10^–6 M, the ED₅₀ was 10^–5 M, and the optimal concentration of between 10^–4 to 10^–3 M released 80% of the total histamine. Kinetensin was 10 to 100 times less potent than neurotensin and equipotent with the opioid peptide dynorphin. The histamine release was clearly temperature-dependent, with no release occurring at 0° or 45°C and with an optimum around 37°C. The histamine release was significantly reduced in the absence of extracellular calcium. Kinetensin also induced a dose-dependent increase in vascular permeability when injected intradermally into rats. The findings indicate that kinetensin is a potent histamine releaser in the rat and may serve as an inflammatory mediator.     

Thirst and vasopressin secretion following central administration of angiotensin II in rats with lesions of the septal area and subfornical organ

Various dipsogenic stimuli, including peripheral and central administration of angiotensin II, have been shown to be capable of releasing vasopressin from the neurohypophyseal system. Studies were carried out in the rat to investigate whether the septal area, which contains a high concentration of angiotensin-sensitive cells and has neural connections with hypothalamic vasopressin-secreting neurons, mediated the stimulatory effect produced by angiotensin II on vasopressin release. Rats with electrolytic lesions in the region of the septal area had increased daily water consumption and urine output when these lesions included the medioventral or lateral nuclei of the septal forebrain, but not when the lesion involved the subfornical organ. No difference was observed in drinking responses following water deprivation or intracerebroventricular injection of angiotensin II in all experimental groups. In addition, the impaired ability to maintain water homeostasis (polyuro-polydipsic syndrome) of septal-lesioned rats was associated septal-lesioned rats was associated with decreased levels of circulating radioimmunoassayable vasopressin. Furthermore, the vasopressin release which occurred in response to intracerebroventricular angiotensin II in normal controls, sham-lesioned and subfornical organ-lesioned rats was significantly attenuated in rats with electrolytic lesion of the medioventral or lateral septal area. Since cells in the lateral septal area are excited by iontophoretic application of angiotensin II, the present data might be consistent with the hypothesis that the stimulatory effect produced by central administration of angiotensin II on vasopressin release rests upon the integrity of the lateral septal area.     

Altered responsivity to central administrations of corticotropin-releasing factor in rats with a history of opiate exposures

The authors studied the effects of a history of opiate exposures on behavioral responses to intracerebroventricular (ICV) microinjections of the stress-related peptide corticotropin-releasing factor (CRF). Rats were injected for 10 days with morphine (10 mg/kg) or saline, and 1 or 7 days later they received an ICV microinjection of CRF (0.5 microg or 2.5 microg) or artificial cerebrospinal fluid. Microinjections of CRF produced anxiety-like behavior, locomotor activity, and self-grooming. The anxiogenic response was altered so that morphine-treated rats showed reduced responses to 0.5-microg CRF but showed exaggerated responses to 2.5-microg CRF 1 or 7 days after last opiate exposure. These findings suggest that alterations in central CRF circuits may underpin the increased vulnerability to anxiety observed following opiate exposures.