Kunikazu Kondo

Neuropeptide FF reduces food intake in rats

The effect of neuropeptide FF (NPFF), a mammalian FMRFamide-like peptide with antiopioid activity, on food intake was investigated in food-deprived rat. The ICV administration of NPFF (5 or 10 micrograms/rat) reduced food intake during the first 60 min after administration. ICV injection of naloxone (10 or 100 micrograms/rat), an opioid antagonist, also decreased food intake. However, the combination of NPFF and naloxone showed no additivity in the anorexigenic effect, suggesting that NPFF and naloxone reduced food intake by the common mechanism. These results indicate that NPFF may function as an endogenous anorexigenic peptide with anitiopioid function.

Aggravation of subclinical diabetes insipidus during pregnancy.

Abstract Background. Transient polyuria and polydip-sia during pregnancy are rare, and their cause is not en-tirely clear. Possible explanations include the exacerba-tion of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity. Methods. We studied two women in whom overt poly-uria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal. Results. One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in re-sponse to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopres-sin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulat-ed plasma vasopressin concentrations were high (16.5 to ...

Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Arginine Vasopressin Release in Conscious Rats

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular (i.c.v.) administration of PACAP raised the plasma AVP concentration in a dose-dependent manner (50-500 pmol/rat), and the maximum effect was obtained at 5 min after the administration. This AVP-releasing effect was not due to a fall of blood pressure, increase of plasma Na or decrease of plasma volume, all of which are known to stimulate AVP release. PACAP had little effect on blood pressure at a low dose, but at higher doses increased it. Vasoactive intestinal peptide (VIP), which is homologous to PACAP, also raised the plasma AVP concentration by i.c.v. injection. An antagonist for VIP receptor, [Lys, Pro, Arg, Tyr]-VIP inhibited the VIP-induced increase of plasma AVP, but had little effect on PACAP-induced increase of plasma AVP. These results suggest that PACAP stimulates AVP release, via specific receptors which are distinct from VIP receptors.

Intracerebroventricular injection of adrenomedullin inhibits vasopressin release in conscious rats

The hypotensive peptide, adrenomedullin (AM), was first isolated from the tissue of human pheochromocytoma. Recently, AM-immunoreactivities have been found in the central nervous system, including the supraoptic and the paraventricular nuclei. In this study, the effect of centrally administered AM on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular injection of AM (1.0 microgram/rat) partially but significantly attenuated the plasma AVP increase induced by hyperosmolality (intraperitoneal (i.p.) injection of hypertonic saline (600 mosmol/kg)) at 30 min after the injection. It also significantly attenuated the plasma AVP increase induced by hypovolemia (i.p. injection of polyethylene glycol) at 30 min after the injection. These results suggest that central AM might play an inhibitory role in both osmo- and baro-regulation of plasma AVP.

Effect of the opioid kappa-receptor agonist U50488H on the secretion of arginine vasopressin. Study on the mechanism of U50488H-induced diuresis.

The effect of U50488H, a potent opioid kappa-receptor agonist, was investigated on the urine volume and on the secretion of arginine vasopressin (AVP) in response to dehydration or hyperosmolar or hypovolemic stimulation in conscious rats. This agonist markedly increased the urine volume in normally hydrated rats and suppressed plasma AVP in a dose-dependent manner in rats given hyperosmolar saline. This suppression of plasma AVP was completely reversed by concurrent injection of naloxone. U50488H also inhibited the release of AVP in dehydrated or hypovolemic rats. These findings indicate that the diuresis induced by U50488H is mainly caused by the suppression of plasma AVP. They also suggest that the kappa-opioid receptor plays an important role in regulating the secretion of AVP.

Anorectic effect of pituitary adenylate cyclase activating polypeptide (PACAP) in rats: lack of evidence for involvement of hypothalamic neuropeptide gene expression.

We investigated the effect of centrally administered pituitary adenylate cyclase activating polypeptide (PACAP) on feeding in rats, and the involvement of hypothalamic neuropeptide gene expression using in situ hybridization. lntracerebroventricular injection of PACAP (1000 pmol/rat) significantly decreased food intake in a dose‐dependent manner. In PACAP‐treated rats, neuropeptide Y (NPY) mRNA levels in the arcuate nucleus and galanin mRNA levels in the paraventricular nucleus increased, and corticotropin‐releasing hormone (CRH) mRNA levels in the paraventricular nucleus decreased. In rats fasted for 72 h, NPY mRNA levels increased, and CRH mRNA levels decreased, but galanin mRNA levels were unchanged. These results indicate that the anorectic function of PACAP is not mediated by NPY or CRH, and that PACAP increases galanin synthesis.

Centrally administered galanin inhibits osmotically stimulated arginine vasopressin release in conscious rats

The effect of centrally administered galanin on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular injection of porcine galanin suppressed hypertonic saline-induced increase in plasma AVP in a dose-dependent manner (12.5-100 pmol/rat) at 10 min after the injection. Pretreatment with subcutaneous injection of naloxone (1 mg/100 g b.wt.) partially blocked the galanin-induced effect on plasma AVP. These results suggest that central galanin inhibits osmotically stimulated AVP release and endogenous opioids are, at least in part, involved in the mechanism.

Osmoregulation of plasma vasopressin in diabetes mellitus with sustained hyperglycemia.

We studied osmoregulation of plasma vasopressin in 5 patients with newly diagnosed diabetes mellitus. All patients showed typical symptoms of uncontrolled diabetes mellitus such as marked hyperglycemia, polyuria, and polydipsia, but did not have advanced diabetic complications. Vasopressin release was studied using 5% hypertonic saline infusion test twice: before treatment when the patient was hyperglycemic, and after treatment 1 to 2 months later when the patient was euglycemic. Plasma vasopressin was measured by a sensitive and specific radioimmunoassay. The mean basal plasma vasopressin value in the patients was significantly higher in the hyperglycemic compared with the euglycemic state (3.75±0.70 vs 1.18±0.46 pmol/l, respectively; P<0.05). The relationship of plasma vasopressin with serum sodium, but not plasma osmolality, during hyperglycemia showed an apparent hypersecretion of vasopressin. In both cases, the sensitivity of the vasopressin response to osmotic stimuli was significantly decreased. During euglycemia, the sensitivity of vasopressin secretion to either sodium or osmolality was almost normal, although a slight rise in the osmostat was observed compared with normal subjects. Together, we found that the positive correlation of vasopressin with sodium or osmolality is maintained but significantly altered in patients with untreated diabetes mellitus. Especially noteworthy is the lowered threshold and decreased sensitivity of osmotically‐induced vasopressin secretion during hyperglycemia, which may be caused by multiple factors such as diabetes‐associated hypovolemia, osmogenic effects of glucose and other osmoles, depletion of the pool of vasopressin available for release, and the metabolic derangement of osmoreceptor/magnocellular neurons.

Galanin as a Physiological Neurotransmitter in Hemodynamic Control of Arginine Vasopressin Release in Rats

Previous neuroanatomical studies have revealed a localization of galanin in several nuclei in the brain stem which are involved in the hemodynamic control of arginine vasopressin (AVP) release. The present study, therefore, investigates the contribution of endogenous galanin to the plasma volume-mediated control of AVP release in conscious rats. Injection of synthetic rat galanin (12.5-50 pmol/rat) into the cisterna magna (i.c.s.) suppressed plasma AVP increased by polyethylene glycol-induced hypovolemia (2.45 +/- 0.24 pg/ml at 50 pmol/rat vs. the vehicle group 5.72 +/- 0.69 pg/ml, p < 0.01). In contrast, when plasma AVP was suppressed by isotonic plasma volume expansion, immunoneutralization of endogenous galanin by antigalanin-antibody i.c.s. significantly reversed the suppression (1.02 +/- 0.07 pg/ml vs. vehicle group 0.63 +/- 0.05 pg/ml, p < 0.01) without altering the mean arterial blood pressure. These results suggest that endogenous galanin is physiologically involved in the plasma volume-mediated control of AVP release through an inhibitory action on this pathway.

The expression of pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA in rat brain: possible role of endogenous PACAP in vasopressin release.

We investigated the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA in rat brain by in situ hybridization. PACAP mRNA was prominently expressed in arcuate nucleus (ARC). Three days of water deprivation significantly increased plasma arginine vasopressin and markedly potentiated the expression of PACAP mRNA in ARC. These results suggest that PACAP in ARC may play some physiological role, possibly one of which may be the control of vasopressin release.