Effect of histamine on the secretion of pro-opiomelanocortin derived peptides in rats

1988 ◽  
Vol 119 (2) ◽  
pp. 312-319 ◽  
Author(s):  
Ulrich Knigge ◽  
Flemming W. Bach ◽  
Steen Matzen ◽  
Peter Bang ◽  
Jørgen Warberg
Keyword(s):  
Receptor Antagonist ◽  
Anterior Pituitary ◽  
Plasma Concentrations ◽  
Gel Filtration ◽  
Male Rats ◽  
Minor Role ◽  
Plasma Acth ◽  
Intracerebroventricular Infusion ◽  
A Minor ◽  
Two Peaks

Abstract. In conscious male rats intracerebroventricular infusion of histamine increased the plasma concentrations of ACTH and β-endorphin immunoreactivity 2.5-fold (P < 0.01). Gel filtration of plasma revealed two peaks of β-endorphin immunoreactivity corresponding to β-endorphin and β-lipotropin. The two fractions increased almost equally in histamine-stimulated animals, whereas most of the circulating β-endorphin immunoreactivity in control animals corresponded to β-endorphin. Central infusion of the H1-receptor agonist 2-thiazolylethylamine and of the H2-receptor agonists dimaprit or 4-methylhistamine increased the plasma ACTH and β-endorphin immunoreactivity concentrations 2- and 3-fold, respectively (P < 0.01). Infused intracerebroventricularly, the H2-receptor antagonists cimetidine or ranitidine prevented the histamine-induced increase in plasma ACTH and β-endorphin immunoreactivity (P < 0.01), whereas the H1-receptor antagonist mepyramine inhibited the peptide responses by 70% (P < 0.01). Infused intra-arterially cimetidine or ranitidine inhibited the histamine-induced increase in plasma ACTH by 80% (P < 0.01) and plasma β-endorphin immunoreactivity by 45% (P < 0.05), whereas mepyramine or the other H1-receptor antagonist SKF-93944 inhibited the ACTH response by 50% (P < 0.05), but had no effect on the β-endorphin immunoreactivity. The results indicate that histamine increases the release of the pro-opiomelanocortin derived peptides ACTH, β-lipotropin and β-endorphin from the anterior pituitary lobe, whereas an effect of histamine on the release of β-endorphin from the neurointermediate lobe is possible. The effect of histamine seems primarily mediated by H2-receptors, whereas H 1-receptors appear to play a minor role.

Cimetidine-induced prolactin release in rats The effect of sex and gonadal steroids

1987 ◽  
Vol 114 (2) ◽  
pp. 178-184 ◽  
Author(s):  
Hajime Watanobe ◽  
Kazuo Takebe
Keyword(s):  
Anterior Pituitary ◽  
Male Rats ◽  
Minor Role ◽  
Adult Males ◽  
Adult Age ◽  
Significant Difference ◽  
Males And Females ◽  
Plasma Prl ◽  
A Minor

Abstract. The cimetidine-induced plasma Prl response was examined in rats of both sexes. First, 10 week old intact adult males and females (dioestrous) were compared. There was no significant difference in the Prl response to cimetidine between the two groups, despite the fact that in adult females the anterior pituitary Prl content was 4 times greater than in males. Second, the effect of gonadal state in adult age on the Prl response to cimetidine was examined in both sexes. In male rats, gonadectomy at the age of 6 weeks significantly reduced the plasma Prl response as well as the pituitary Prl content, both of which were sufficiently restored by testosterone replacement. However, in females, neither gonadectomy at the age of 6 weeks nor subsequent oestradiol replacement affected the Prl response to cimetidine, despite the fact that gonadectomy significantly reduced and oestradiol treatment significantly enhanced the pituitary Prl content. Third, possible permanent effects of the postnatal gonadal milieu on the cimetidine-induced Prl response and the pituitary Prl content were examined in both sexes by castration at varying postnatal ages. The ratio of plasma Prl response to pituitary Prl content was similar in all castrated males. In females, however, the ratio decreased with increasing castration age. In conclusion, the mechanism of cimetidine-induced Prl release is less sex-dependent than are the mechanisms of Prl release by other Prl secretagogues. First, this may be due to a minor role of oestrogen in females in determining the Prl response to cimetidine. Second, the postnatal ovarian secretions may exert a permanent inhibition of the development of the cimetidine-mobilized anterior pituitary Prl pool.

Adrenal and gonadal function in hypothyroid adult male rats

1997 ◽  
Vol 152 (1) ◽  
pp. 147-154 ◽  
Author(s):  
A Tohei ◽  
M Akai ◽  
T Tomabechi ◽  
M Mamada ◽  
K Taya
Keyword(s):  
Adult Male ◽  
Functional Relationship ◽  
Plasma Concentrations ◽  
Gonadal Hormones ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Male Rats ◽  
Plasma Acth ◽  
Corticosterone Release ◽  
Acth Release

Abstract The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouracil-treated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH. Journal of Endocrinology (1997) 152, 147–154

Feeding behavior in the nocturnal moth Manduca sexta is mediated mainly by blue receptors, but where are they located in the retina?

1995 ◽  
Vol 198 (9) ◽  
pp. 1909-1917 ◽  
Author(s):  
D Cutler ◽  
R Bennett ◽  
R Stevenson ◽  
R White
Keyword(s):  
Manduca Sexta ◽  
Spectral Sensitivity ◽  
Compound Eye ◽  
Action Spectrum ◽  
Minor Role ◽  
Feeding Response ◽  
Small Areas ◽  
Nectar Feeding ◽  
A Minor ◽  
Two Peaks

The spectral sensitivity of nectar feeding by adults of the tobacco hawkmoth Manduca sexta was measured in free-choice experiments. The action spectrum displayed a narrow peak at 450 nm and a low secondary maximum at 560 nm. Thus, the feeding response is mediated primarily by blue-sensitive receptors containing the Manduca sexta photopigment P450, while green-sensitive receptors containing P520 play a minor role. A minimum at 500 nm separating the two peaks suggests mutual inhibition between green and blue receptors or negative interaction more proximally in the visual system. The action spectrum drops off abruptly at 400 nm, in accordance with an earlier finding that ultraviolet wavelengths, discerned by receptors containing P357, obstruct the feeding response. The spectral sensitivity of the Manduca sexta compound eye, determined by electroretinogram recordings, and earlier visual pigment measurements indicate that approximately 75 % of the receptors are green-sensitive, with the remainder divided between blue- and ultraviolet-sensitive cells. The distribution of receptor types in small areas of the retina was measured by their ultrastructural response to light. Green and ultraviolet receptors were found, but not the blue receptors that dominate the feeding response. Possibly they are concentrated in a particular region of the retina that has not yet been found.

Effect of exogenous β-endorphin on anterior pituitary hormone secretion in man

1982 ◽  
Vol 99 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Tsutomu Oyama ◽  
Ryuji Yamaya ◽  
Toshiro Jin ◽  
Tsuyoshi Kudo
Keyword(s):  
Growth Hormone ◽  
Anterior Pituitary ◽  
Human Subjects ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Adrenocortical Function ◽  
Control Group ◽  
Pituitary Hormone ◽  
Plasma Acth ◽  
Anterior Pituitary Hormone

Abstract. The effect of large amounts of synthesized human β-endorphin (β-Ep) administered intrathecally on pituitary-adrenocortical function was investigated by determining the plasma levels of ACTH, cortisol, growth hormone and prolactin in 8 patients with pain caused by severe disseminated cancer. They were divided into 2 groups, an Ep group of 8 patients and a control group of 5 of the same 8 patients. There were no significant effects of β-Ep on plasma ACTH, cortisol and growth hormone levels. However, the injection of β-Ep into human subjects resulted in a rise in plasma concentrations of prolactin.

Acute and short-term actions of serotonin administration on the pituitary-testicular axis in the adult rat

1995 ◽  
Vol 7 (5) ◽  
pp. 1101 ◽  
Author(s):  
MP Hedger ◽  
S Khatab ◽  
G Gonzales ◽  
Kretser DM de
Keyword(s):  
Serum Testosterone ◽  
Fold Increase ◽  
Significant Inhibition ◽  
Male Rats ◽  
Minor Role ◽  
Testis Weight ◽  
Serum Concentrations ◽  
Adult Rat ◽  
Serum Lh ◽  
A Minor

In this study, adult male rats were injected intraperitoneally with a single dose of serotonin (5-hydroxytryptamine, 5HT; 10 mg kg-1 bodyweight) for 2 h or 18 h, or daily with graded doses of 5HT (0.1-10 mg kg-1) for four days before being killed. Serum and testicular interstitial fluid (IF) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and immunoreactive-inhibin were measured by radioimmunoassay, and one testis was removed for histological examination. At 2 h after a single injection, 5HT caused a significant inhibition of serum concentrations of LH and inhibin, recovered IF volume and intratesticular testosterone concentrations; testis weight and serum concentrations of testosterone and FSH were unaffected. At 18 h after injection, all parameters had returned to normal, with the exception of intratesticular testosterone concentration which remained lower than normal. The lowest 5HT dose (0.1 mg kg-1) had no effect on any parameter following four daily injections. At a dose of 1.0 mg kg-1 5HT, there was a four-fold increase in the concentration of serum LH, but testis weight, recovered IF volume, testosterone and inhibin concentrations and serum concentrations of FSH were not significantly affected. At the highest dose of 5HT (10 mg kg-1) after four daily injections, testis weight decreased, and IF volume increased nearly three-fold. Testis concentrations of inhibin and serum testosterone were reduced, whereas serum concentrations of both LH and FSH were elevated; intratesticular testosterone concentrations did not differ from controls. Only at the highest dose of 5HT was disruption to the seminiferous epithelium observed, with focal damage ranging in severity from increased degeneration of spermatogenic cell profiles, to complete loss of the germinal epithelium; however, many tubule profiles displayed completely normal spermatogenesis. The acute IF volume reduction and spermatogenic disruption in 5HT-treated rats were consistent with localized ischaemia due to constriction of the testicular arterial supply. The eventual increase in IF volume observed after 5HT treatment appeared to be secondary to the loss of germ cells. Although 5HT also inhibited pituitary LH release and Leydig cell steroidogenesis, these effects appeared to play only a minor role in the induction of spermatogenic damage.

The pharmacokinetics of azacitidine following subcutaneous treatment in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7087-7087
Author(s):  
E. Laille ◽  
R. Ward ◽  
A. Nasser ◽  
M. Stoltz ◽  
C. Cogle ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
Hepatic Metabolism ◽  
Volume Of Distribution ◽  
Adverse Event Reporting ◽  
Myelogenous Leukemia ◽  
Minor Role ◽  
Renal Elimination ◽  
Drug Concentrations ◽  
A Minor

7087 Background: 5-azacitidine (AZA), through its effects on DNA metabolism, gene expression, and cell differentiation, has proven beneficial in treatment of MDS and AML and AZA therapy significantly increases survival in higher-risk MDS and AML compared to conventional care. Few studies have evaluated the pharmacokinetics (PK) of AZA and the renal elimination of AZA has not been previously published to our knowledge. Plasma PK of AZA are herein reported in patients receiving SC doses of 75 mg/m2. This study was designed to also assess the contribution of renal elimination to the overall clearance of AZA. Methods: Adult patients with MDS or AML and ECOG status 0–2 were treated with 7 consecutive daily SC doses of 75 mg/m2 AZA during their first treatment cycle. PK parameters of AZA were derived from drug concentrations in plasma and urine collected after the first and last dose (day 7) of AZA. Safety was evaluated by adverse event reporting (NCI-CTC). Results: Currently, 18 patients have been treated with SC AZA. AZA was rapidly absorbed and reached peak plasma concentrations (concs) within 0.5 hr post dosing. The AUCinf after SC doses was 1170 hr*ng/mL. The AZA concs declined in a pseudo bi-phasic manner with an elimination half-life of 1.25 hours. The plasma PK profiles after the first and last dose were superimposable. The apparent total clearance (CL/F) and volume of distribution (Vd/F) were 143 L/hr and 318 L, respectively. AZA recovery in urine was very small relative to dose (<2%). AZA was well tolerated and no unexpected toxicities were observed. Conclusions: The AZA AUCinf after SC doses is similar to the published AUC value (1044 hr*ng/mL) after 75 mg/m2 IV doses indicating approximating 100% systemic bioavailability. After SC dosing, CL/F exceeded hepatic blood flow indicating extra-hepatic metabolism. Vd/F was 4–5 fold greater than total body water suggesting extensive AZA tissue distribution. Renal elimination appears to play a minor role in the overall clearance of AZA. [Table: see text]

scholarly journals Effect of blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 receptors on catecholamine-induced stimulation of ACTH and prolactin secretion

2000 ◽  
pp. 637-641 ◽  
Author(s):  
E Willems ◽  
U Knigge ◽  
H Jorgensen ◽  
A Kjaer ◽  
J Warberg
Keyword(s):  
Receptor Antagonist ◽  
Prolactin Secretion ◽  
Male Rats ◽  
H2 Receptor Antagonist ◽  
Histaminergic System ◽  
Intracerebroventricular Infusion ◽  
H2 Receptors ◽  
H3 Receptors ◽  
Prolactin Response ◽  
Stimulation Of

The effect of inhibition of the neuronal histaminergic system by blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 autoreceptors on the ACTH and prolactin responses to the catecholamines epinephrine and norepinephrine was investigated in conscious male rats. Intracerebroventricular infusion of epinephrine and norepinephrine stimulated ACTH and prolactin secretion. Prior intracerebroventricular infusion of the H1 receptor antagonist, mepyramine, or the H2 receptor antagonist, cimetidine, had no effect on the ACTH response to epinephrine or norepinephrine, while these responses were inhibited by pretreatment with the H3 receptor agonist, imetit. The prolactin response to norepinephrine was significantly inhibited by pretreatment with mepyramine, cimetidine or imetit whereas the three histaminergic compounds had no effect on the prolactin response to epinephrine. The findings suggest that the histaminergic system exerts a mediating or permissive action on the norepinephrine-induced stimulation of prolactin secretion, whereas an intact histaminergic system may not be required for catecholamines to stimulate ACTH secretion. The inhibitory effect of imetit on catecholamine-induced release of ACTH may be due to an activation of H3 receptors located presynaptically on non-histaminergic neurons, e.g. aminergic neurons. The study further indicates an important role of histamine in the neuroendocrine regulation of prolactin secretion.

Characterization of Native Human Thrombopoietin in the Blood of Normal Individuals and of Patients with Haematologic Disorders

1999 ◽  
Vol 82 (07) ◽  
pp. 24-29 ◽  
Author(s):  
Atsushi Matsumoto ◽  
Tomoyuki Tahara ◽  
Haruhiko Morita ◽  
Kensuke Usuki ◽  
Hideya Ohashi ◽  
...  
Keyword(s):  
Size Distribution ◽  
Gel Filtration ◽  
Molecular Size ◽  
Immunoblot Analysis ◽  
Biologically Active ◽  
Amino Acid Residues ◽  
Normal Individuals ◽  
Normal Human ◽  
A Minor ◽  
Two Peaks

SummaryThrombopoietin (TPO) isolated from thrombocytopenic plasma of various animal species has previously been shown to comprise only truncated forms of the molecule, presumably generated by proteolysis. Native TPO has now been partially purified from normal human plasma by immunoaffinity chromatography and was confirmed to be biologically active. Gel filtration in the presence of SDS revealed that TPO eluted in two peaks: a major peak corresponding to the elution position of fully glycosylated recombinant human TPO (rhTPO) consisting of 332 amino acid residues, and a minor peak corresponding to a smaller molecular size. Immunoblot analysis also revealed that most plasma-derived TPO migrated at the same position as fully glycosylated rhTPO, corresponding to a molecular size of ~80 to 100 kDa. Furthermore, the size distribution of circulating TPO in patients with various haematologic disorders did not differ markedly from that of plasma-derived TPO from healthy individuals. These results indicate that the truncation of circulating TPO is not related to disease pa-thophysiology, and that the predominant form of TPO in blood is a biologically active ~80- to 100-kDa species. The size distribution of TPO extracted from normal platelets was similar to that of TPO in plasma; the proportion of truncated TPO was decreased by prior incubation of platelets with hirudin, indicating that the endogenous truncated TPO, at least in platelet extract, was generated by thrombin-mediated cleavage.

Binding Of Thrombin By Plasma Inhibitors

1981 ◽  
Author(s):  
J A Penner ◽  
H I Hassouna
Keyword(s):  
Experimental Approach ◽  
Specific Activity ◽  
Binding Capacity ◽  
Gel Filtration ◽  
Minor Role ◽  
Clotting System ◽  
Chloramine T ◽  
Presence And Absence ◽  
A Minor

Our study was undertaken with the purpose of clarifying the role of plasma inhibitors other than antithrombin III (ATIII) in binding thrombin in the presence and absence of heparin. In the clotting system, several antiproteinases are involved in neutralizing active factors. The capacity to destroy thrombin is attributed to ATIII whose concentration in plasma is ten times less than α1 antitrypsin (α1A) . If heparin is added to plasma, ATIII becomes an immediate inhibitor of thrombin. Several studies have indicated that a modest depression in ATIII activity leads to thrombosis, inferring that other plasma antiproteinases play a minor role. Experimental approach was as follows: Defibrinated platelet poor citrated human plasma was depleted of ATIII and α1 by means of monospecific insolubilized antibodies. Purified thrombin, labelled by Chloramine T incorporation of 125I in NaOH, had a specific activity of 1.3 × 105 CPM/μg. Total antiproteinase thrombin binding capacity of defibrinated plasma was estimated by incubating 4 × 10-33 μM thrombin with plasma (100 μl) for 2 hours and 24 hours in the absence of heparin and for 5 minutes in the presence of heparin (20 units). Free from bound *thrombin was separated by gel filtration on Sephacryl S200 and chromatograms monitored on gamma analyzer. Following the same protocol, ATIII deficient plasma was used to evaluate thrombin binding capacity not attributable to ATIII, and role of ATIII in the absence of α1A was assessed in α1A depleted plasma. As a result, ATIII binding capacity was found to be 62 μg *thrombin/100 μl of normal and α1A deficient plasma, in the presence and absence of heparin, eluting at a volume corresponding to 9 × 104 daltons. Binding capacity of other plasma inhibitors in ATIII deficient plasma amounted to 24 μg *thrombin in the absence of heparin and 7 μg in its presence. This confirms the role of ATIII as the major antithrombin, heparin cofactor. In its absence inactivation of thrombin is reduced by 61%.

scholarly journals No Evidence That RFamide-Related Peptide 3 Directly Modulates LH Secretion in the Ewe

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1566-1575 ◽  
Author(s):  
C. Decourt ◽  
K. Anger ◽  
V. Robert ◽  
D. Lomet ◽  
J. Bartzen-Sprauer ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Estradiol Benzoate ◽  
Inhibitory Effect ◽  
Minor Role ◽  
Gonadotropin Secretion ◽  
Related Peptide ◽  
Lh Pulsatility ◽  
Lh Release ◽  
A Minor ◽  
Lh Secretion

Abstract The neuropeptide RFamide-related peptide 3 (RFRP-3) has been implicated in the control of gonadotropin secretion in both birds and mammals. However, in mammals, depending on species, sex and photoperiod, inhibitory, excitatory, or no effect of RFRP-3 on the plasma concentration of LH has been reported. In the ewe, treatment with RFRP-3 either reduced LH concentration or had no effect, and treatment with an RFRP-3 receptor antagonist (ie, RF9) resulted in increased concentration of plasma LH. To clarify these conflicting results in the present study, a set of experiments was performed in ewes. Multiple iv injections of RFRP-3 (6 × 50 μg) in ovariectomized ewes had no effect on plasma LH pulsatility. In intact ewes a bolus injection (500 μg) or an injection (250, 500, or 1000 μg) followed by a 4-hour perfusion (250, 500, or 1000 μg · h−1) of RFRP-3 had no effect on the LH pulse induced by kisspeptin (6.5 μg). In ovariectomized, estrogen-replaced ewes, the LH surge induced by estradiol benzoate was not modified by a 24-hour perfusion of RFRP-3 (500 μg h−1). Finally, although treatment with RF9 induced a robust release of LH, treatment with a more selective RFRP-3 receptor antagonist, GJ14, resulted in no evident increase of LH. In contrast to the inhibitory effect previously suggested, our data are more consistent with the concept that RFRP-3 has no direct effect on LH secretion in ewes and that RF9 effect on LH release is likely not RFRP-3 receptor mediated. Hence, RFRP-3 probably has a minor role on the control of LH secretion in the ewe.

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