C-type Natriuretic Peptide Inhibits L-type Ca2+ Current in Rat Magnocellular Neurosecretory Cells by Activating the NPR-C Receptor

2005 ◽  
Vol 94 (1) ◽  
pp. 612-621 ◽  
Author(s):  
Robert A. Rose ◽  
Madhu B. Anand-Srivastava ◽  
Wayne R. Giles ◽  
Jaideep S. Bains
Keyword(s):  
Natriuretic Peptide ◽  
Action Potentials ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Neurosecretory Cells ◽  
Mediated Effects ◽  
Inhibitory G Protein ◽  
Whole Cell Recordings ◽  
Supraoptic Nuclei

Magnocellular neurosecretory cells (MNCs), of the paraventricular and supraoptic nuclei of the hypothalamus, secrete the hormones vasopressin and oxytocin. As a result, they have an essential role in fundamental physiological responses including regulation of blood volume and fluid homeostasis. C-type natriuretic peptide (CNP) is present at high levels in the hypothalamus. Although CNP is known to decrease hormone secretion from MNCs, no studies have examined the role of the natriuretic peptide C receptor (NPR-C) in these neurons. In this study, whole cell recordings from acutely isolated MNCs, and MNCs in a coronal slice preparation, show that CNP (2 × 10−8 M) and the selective NPR-C agonist, cANF (2 × 10−8 M), significantly inhibit L-type Ca2+ current ( ICa(L)) by ∼50%. This effect on ICa(L) is mimicked by dialyzing a Gi-activator peptide (10−7 M) into these cells, implicating a role for the inhibitory G protein, Gi. These NPR-C–mediated effects were specific to ICa(L). T-type Ca2+ channels were unaffected by CNP. Current-clamp experiments revealed the ability of CNP, acting via the NPR-C receptor, to decrease (∼25%) the number of action potentials elicited during a 500 ms depolarizing stimulus. Analysis of action potential duration revealed that CNP and cANF significantly decreased 50% repolarization time (APD50) in MNCs. In summary, our findings show that CNP has a potent and selective inhibitory effect on ICa(L) and on excitability in MNCs that is mediated by the NPR-C receptor. These data represent the first electrophysiological evidence of a functional role for the NPR-C receptor in the mammalian hypothalamus.

POSSIBLE ROLE OF 5α-ANDROSTANE-3α,17β-DIOL IN THE CONTROL OF FOLLICLE-STIMULATING HORMONE SECRETION IN THE IMMATURE FEMALE RAT

1982 ◽  
Vol 92 (1) ◽  
pp. 37-42 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER ◽  
L. GRIBLING-HEGGE
Keyword(s):  
Inhibitory Action ◽  
Combined Treatment ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Immature Rat ◽  
Rat Strain ◽  
Intact Rats

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.

scholarly journals Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3071 ◽  
Author(s):  
Giustino Orlando ◽  
Sheila Leone ◽  
Claudio Ferrante ◽  
Annalisa Chiavaroli ◽  
Adriano Mollica ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Reproductive Function ◽  
Inhibitory Effect ◽  
Bdnf Gene ◽  
Appetite Control ◽  
Hydroxyindoleacetic Acid ◽  
Puberty Onset

Besides its role as key regulator in gonadotropin releasing hormone secretion, reproductive function, and puberty onset, kisspeptin has been proposed to act as a bridge between energy homeostasis and reproduction. In the present study, to characterize the role of hypothalamic kisspeptin as metabolic regulator, we evaluated the effects of kisspeptin-10 on neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) gene expression and the extracellular dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIIA) concentrations in rat hypothalamic (Hypo-E22) cells. Our study showed that kisspeptin-10 in the concentration range 1 nM–10 μM was well tolerated by the Hypo-E22 cell line. Moreover, kisspeptin-10 (100 nM–10 μM) concentration independently increased the gene expression of NPY while BDNF was inhibited only at the concentration of 10 μM. Finally, kisspeptin-10 decreased 5-HT and DA, leaving unaffected NE levels. The inhibitory effect on DA and 5-HT is consistent with the increased peptide-induced DOPAC/DA and 5-HIIA/5-HT ratios. In conclusion, our current findings suggesting the increased NPY together with decreased BDNF and 5-HT activity following kisspeptin-10 would be consistent with a possible orexigenic effect induced by the peptide.

scholarly journals The Complex World of Regulation of Pituitary Growth Hormone Secretion: The Role of Ghrelin, Klotho, and Nesfatins in It

2021 ◽  
Vol 12 ◽  
Author(s):  
Jesús Devesa
Keyword(s):  
Energy Homeostasis ◽  
Direct Action ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cytosolic Calcium ◽  
Inhibitory Effect ◽  
Complex World ◽  
Gh Secretion ◽  
Acyl Ghrelin

The classic concept of how pituitary GH is regulated by somatostatin and GHRH has changed in recent years, following the discovery of peripheral hormones involved in the regulation of energy homeostasis and mineral homeostasis. These hormones are ghrelin, nesfatins, and klotho. Ghrelin is an orexigenic hormone, released primarily by the gastric mucosa, although it is widely expressed in many different tissues, including the central nervous system and the pituitary. To be active, ghrelin must bind to an n-octanoyl group (n = 8, generally) on serine 3, forming acyl ghrelin which can then bind and activate a G-protein-coupled receptor leading to phospholipase C activation that induces the formation of inositol 1,4,5-triphosphate and diacylglycerol that produce an increase in cytosolic calcium that allows the release of GH. In addition to its direct action on somatotrophs, ghrelin co-localizes with GHRH in several neurons, facilitating its release by inhibiting somatostatin, and acts synergistically with GHRH stimulating the synthesis and secretion of pituitary GH. Gastric ghrelin production declines with age, as does GH. Klotho is an anti-aging agent, produced mainly in the kidneys, whose soluble circulating form directly induces GH secretion through the activation of ERK1/2 and inhibits the inhibitory effect that IGF-I exerts on GH. Children and adults with untreated GH-deficiency show reduced plasma levels of klotho, but treatment with GH restores them to normal values. Deletions or mutations of the Klotho gene affect GH production. Nesfatins 1 and 2 are satiety hormones, they inhibit food intake. They have been found in GH3 cell cultures where they significantly reduce the expression of gh mRNA and that of pituitary-specific positive transcription factor 1, consequently acting as inhibitors of GH production. This is a consequence of the down-regulation of the cAMP/PKA/CREB signaling pathway. Interestingly, nesfatins eliminate the strong positive effect that ghrelin has on GH synthesis and secretion. Throughout this review, we will attempt to broadly analyze the role of these hormones in the complex world of GH regulation, a world in which these hormones already play a very important role.

Role of atrial natriuretic peptide in natriuresis in volume-expanded rats

1987 ◽  
Vol 253 (6) ◽  
pp. R877-R882
Author(s):  
K. Kaneko ◽  
K. Okada ◽  
S. Ishikawa ◽  
T. Kuzuya ◽  
T. Saito
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Critical Role ◽  
Hormone Secretion ◽  
Isotonic Saline ◽  
Fold Increase ◽  
Urinary Sodium Excretion ◽  
Inappropriate Antidiuretic Hormone Secretion ◽  
Atrial Natriuretic

Continuous intravenous infusion of rat atrial natriuretic peptide (rANP) was carried out for 60 min in urethan-anesthetized rats. Plasma rANP (PANP) levels during 0, 12.5, and 50 ng/min rANP infusion reached 20.9 +/- 3.4, 61.2 +/- 12.3, and 228 +/- 30.6 pg/ml, respectively. Urinary sodium excretion (UNaV) remained unchanged during the 0 and 12.5 ng/min rANP infusion. In contrast, the 50 ng/min rANP infusion resulted in a 5.6-fold increase in UNaV without significant changes in plasma aldosterone levels and glomerular filtration rate. Isotonic saline infusion (116 microliter/min for 60 or 120 min) caused a significant increase in UNaV. UNaV in an experimental model of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was 5.0 times greater than in control animals. PANP levels in 60- or 120-min saline-infused and SIADH rats were 46.3 +/- 6.7, 39.0 +/- 9.0, and 35.6 +/- 3.2 pg/ml, respectively. These values were significantly higher than control values but failed to achieve a level at which natriuresis occurred during the infusion of rANP. These results suggest that endogenous ANP may not play a critical role in the induction of acute natriuresis in volume-expanded states, although it could be partially involved in such a natriuretic response.

Atrial natriuretic peptide-induced inhibition of aldosterone secretion: a quest for mediator(s)

1992 ◽  
Vol 263 (2) ◽  
pp. E181-E194 ◽  
Author(s):  
A. Ganguly
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Biological Effects ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Calcium Flux ◽  
Aldosterone Secretion ◽  
Adrenal Cells ◽  
Inhibitory G Protein ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) inhibits aldosterone secretion evoked by its physiological secretagogues by a mechanism(s) likely to involve intracellular messengers. When one examines the results of various investigations so far, this premise, although not definitive yet, seems to be supported. Therefore a brief perspective on the cellular messengers of the various secretagogues is provided before the inquiry into the possible mechanism of action of ANP. The receptors of ANP in the adrenal cells have been identified and characterized. ANP inhibits adenylate cyclase in various tissues through an inhibitory G protein, which appears to explain in part the inhibitory effect of ANP on adrenocorticotropin-induced aldosterone secretion. However, there could be other possible effects of ANP as discussed. ANP probably inhibits aldosterone secretion evoked by angiotensin II and potassium by interfering with the appropriate changes in calcium flux and cell calcium concentration, concomitants of stimulation by these secretagogues. The potential modes of these effects are probed. The role of guanosine 3',5'-cyclic monophosphate, which is increased by receptor activation of guanylate cyclase by ANP and is thought to play a major role in the biological effects of ANP in some other tissues, remains controversial in the aldosterone-lowering effect of ANP, and this is also discussed extensively in this review.

Non-NMDA and NMDA receptors in the synaptic pathway between area postrema and nucleus tractus solitarius

1998 ◽  
Vol 275 (4) ◽  
pp. H1236-H1246 ◽  
Author(s):  
Maria Luz Aylwin ◽  
John M. Horowitz ◽  
Ann C. Bonham
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Action Potentials ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Slow Component ◽  
Nmda Receptor Antagonist ◽  
Afferent Information ◽  
Whole Cell Recordings

Area postrema (AP) modulates cardiovascular function through excitatory projections to neurons in nucleus tractus solitarius (NTS), which also process primary sensory (including cardiovascular-related) input via the solitary tract (TS). The neurotransmitter(s) and their receptors in the AP-NTS pathway have not been fully characterized. We used whole cell recordings in voltage- and current-clamp modes in the rat brain stem slice to examine the role of ionotropic glutamatergic receptors and α2-adrenergic receptors in the pathway from AP to NTS neurons receiving visceral afferent information via the TS. In neurons voltage clamped at potentials from −100 to +80 mV, AP stimulation (0.2 Hz) evoked excitatory postsynaptic currents having a fast component blocked by the non- N-methyl-d-aspartate (NMDA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulfonamide (NBQX; 3 μM, n = 7) and a slow component blocked by the NMDA receptor antagonistdl-2-amino-5-phosphonovaleric acid (APV; 50 μM, n = 8). Although NBQX (3 μM, n = 14) abolished AP-evoked action potentials, APV (50 μM, n = 9 or 500 μM, n = 6) or yohimbine, (200 nM, n = 5 or 2 μM, n = 10) did not. Thus, although AP stimulation activates both non-NMDA and NMDA receptors on NTS neurons receiving TS input, only non-NMDA receptors are required for synaptic transmission.

Physiological role of thiol proteases in thyroid hormone secretion

1986 ◽  
Vol 113 (2) ◽  
pp. 261-267 ◽  
Author(s):  
Mototaka Yoshinari ◽  
Alvin Taurog
Keyword(s):  
Density Gradient ◽  
Gradient Centrifugation ◽  
Polyacrylamide Gel Electrophoresis ◽  
Hormone Secretion ◽  
Physiological Role ◽  
Inhibitory Effect ◽  
Thiol Proteases ◽  
Presence And Absence ◽  
Rat Thyroid

Abstract. To determine the physiological role of the thiol proteases in T4 and T3 release from thyroglobulin, experiments were performed with 131I-prelabelled rat thyroid lobes incubated in vitro in the presence and absence of leupeptin, an inhibitor of thiol proteases. Basal secretion of [131I]T4 and [131I]T3 from rat thyroid lobes prelabelled in vivo was quite low, but in the presence of 10 mU/ml bovine TSH a marked stimulatory effect was observed. The stimulatory effect of TSH was completely abolished by leupeptin. This was associated with marked inhibition of lysosomal proteolytic activity, suggesting that the inhibitory effect of leupeptin on T4 and T3 secretion could be attributed to its inhibitory action on proteolysis of thyroglobulin. Further evidence for an inhibitory effect of leupeptin on intralysosomal hydrolysis of thyroglobulin was obtained when thyroid lobes were incubated with 131I- in the presence and absence of leupeptin and TSH. The crude lysosomal preparation was fractionated on a Percoll density gradient, which separates 131I-containing particles into a dense peak containing purified lysosomes and a buoyant peak containing pinocytotic vesicles. A marked increase in the 131I-content of the dense peak was observed in the presence of TSH + leupeptin. Analysis of the 131I in the dense fraction by sucrose density gradient centrifugation and by SDS-polyacrylamide gel electrophoresis demonstrated that leupeptin inhibited degradation of 19S thyroglobulin, especially the formation of [131I]peptides of MW < 14K.

scholarly journals The role of neuropeptide Y and interaction with leptin in regulating feed intake and luteinizing hormone and growth hormone secretion in the pig

Reproduction ◽  
2006 ◽  
Vol 131 (6) ◽  
pp. 1127-1135 ◽  
Author(s):  
C Richard Barb ◽  
Robert R Kraeling ◽  
George B Rampacek ◽  
Gary J Hausman
Keyword(s):  
Neuropeptide Y ◽  
Feed Intake ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Blood Samples ◽  
Gh Secretion ◽  
Lh Secretion ◽  
Serum Gh

Two experiments (EXP) were conducted in ovariectomized prepubertal gilts to test the hypothesis that neuropeptide Y (NPY) stimulates appetite and modulates LH and GH secretion, and that leptin modifies such acute effects of NPY on feeding behavior and LH and GH secretion. In EXP I, gilts received intracerebroventricular (ICV) injections of 0.9% saline (saline; n=6), or 10 μg (n=7), 50 μg (n=5) or 100 μg (n=7) NPY in saline and blood samples were collected. In EXP II, gilts received ICV injections of S (n=4), or 50 μg leptin (n=4), or 100 μg NPY (n=4) or 100 μg NPY +50 μg leptin (n=4) in saline, and feed intake was measured at 4, 20 and 44 h after feed presentation and blood samples collected. In EXP I, NPY suppressed LH secretion and the 100 μg dose stimulated GH secretion. In EXP II, NPY reversed the inhibitory effect of leptin on feed intake and suppressed LH secretion, but serum GH concentrations were unaffected. These results support the hypothesis that NPY modulates feed intake, and LH and GH secretion and may serve as a neural link between metabolic state and the reproductive and growth axis in the pig.

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