摘要:

The dopaminergic inhibition of anterior pituitary adenylate cyclase activity, cAMP accumulation, and prolactin release was studied in the presence of the Ca2+ channel activator, maitotoxin. In isobutylmethylxanthine (IBMX)-treated cells, maitotoxin stimulated prolactin secretion within 30 s and cAMP accumulation within 1 min. Although dopamine reduced cAMP accumulation and prolactin release, the effectiveness of the catecholamine was reduced in the presence of maitotoxin. When hemipituitary glands were exposed for 10 min to 100 ng maitotoxin/ml, their membranes showed increased adenylate cyclase activity. The hypothesis that maitotoxin stimulates adenylate cyclase activity by increasing Ca2+ availability was supported by the observation that, at concentrations up to 100 µM, Ca2+ stimulated anterior pituitary adenylate cyclase acitivity. Although dopamine decreased basal and maitotoxin-stimulated pituitary cAMP accumulation, via changes in adenylate cyclase activity, the decrement in cyclic nucleotide production, but not prolactin release, can be ascribed to the effect of the catecholamine on the basal activities of these parameters. These data provide additional evidence that an increased Ca2+ flux is stimulating to cAMP generation and prolactin release, whereas dopamine is inhibitory to these processes

ISSN:0028-3835    

DOI:10.1159/000124613

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The object of this study was to examine the effect of porcine follicular fluid (PFF) alone or in combination with estradiol (E2) on pulsatile LH release during the interval between the mornings of diestrus 2 (D2) and proestrus in the rat. Steroids were removed from PFF by charcoal extraction. Preliminary studies indicated that 1 ml PFF given intraperitoneally suppressed FSH secretion for up to 15 h, with an onset of action between 3 and 4h and maximal suppression between 6 and 9 h. In subsequent experiments, six groups of animals were bled continuously for 3 h between 07.30 and 10.30 h at a rate of 50 µl whole blood/5 min: group 1 was bled on D2; group 2 was sham ovariectomized on D2 (08.30–09.30 h), immediately implanted with an empty capsule, given saline at 12.00 and 24.00 h, and bled on proestrous AM; groups 3–6 were ovariectomized on D2, implanted with an empty or E2 capsule, given 1 ml saline or PFF at 12.00 and 24.00 h, and bled 24 h following ovariectomy (OVX). Between D2 and proestrus plasma E2 levels increased, and there was no change in any parameter of pulsatile LH release. However, OVX on D2 reduced plasma E2 levels and increased mean blood LH levels above proestrous values due to increases in LH pulse amplitude and frequency. Restoration of physiological proestrous levels of E2 reduced the increase in mean blood LH levels, by lowering pulse frequency to proestrous values and by greatly reducing pulse amplitude. However, LH pulse amplitude and mean blood LH levels were still higher than values on proestrus. PFF alone produced no alteration in any parameter of pulsatile LH release compared with saline-treated animals. However, administration of PFF to E2-implanted rats reduced LH pulse amplitude and mean blood LH levels to proestrous morning values. PFF also suppressed the OVX-induced increase in plasma FSH levels in empty- or E2-capsule implanted rats. Moreover, PFF given to E2-implanted rats significantly reduced the increase in mean blood LH levels seen in response to LHRH in E2, saline-treated animals. These experiments (1) confirm our previous report on the restraining action of E2 on LH pulse amplitude and frequency between the mornings of D2 and proestrus; (2) demonstrate that PFF contains a nonsteroidal substance with the ability to synergize with E2 in the regulation of LH pulse amplitude during this 24-hour interval, and (3) indicate that this restraining action of PFF is exerted, at least in part, at the pituitary l

ISSN:0028-3835    

DOI:10.1159/000124614

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The radiolabeled angiotensin II (ANG II) antagonist, [125I]-sar1, ile8-ANG II, was used to study brain ANG II receptors by both homogenate binding and in vitro autoradiography. In homogenate preparations of the hypothalamus, thalamus, septum and midbrain (HTSM), [125I]-sar1 ile8-ANG II bound to a single class (Hill slope 0.84 ± 0.05) of high affinity binding sites (KD 0.42 ± 0.03 nM, Bmax 5.98 ± fmol/mg protein). Competition for the [125I]-sar1 ile8-ANG II binding site in HTSM membranes demonstrated a rank order potency characteristic of binding to the ANG II receptor, with the unlabeled antagonist being slightly more potent than ANG II (Ki 0.22 ± 0.03 vs. 0.95 ± 0.06 nM, respectively). Brain slices from the region of the rostral third ventricle were incubated with 0.5 nM [125I]-sar1, ile8-ANG II in the presence or absence of 1 µM ANG II and exposed to LKB Ultrofilm. Autoradiographic images of [125I]-sar’, ile8-ANG II binding revealed that structures situated within the anterior wall of the third ventricle, i.e. the lamina terminalis, were heavily labeled; including the subfornical organ, median preoptic nucleus and organum vasculosum laminae terminalis. These results show the utility of [125I]-sar1, ile8-ANG II as a probe to study brain ANG II receptors and provides pharmacological evidence for the rostral third ventricle as a possible site for central ANG II

ISSN:0028-3835    

DOI:10.1159/000124615

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

A specific α2-adrenoceptor antagonist (idazoxan) was used in man to examine the neuroregulation of growth hormone (GH) release and the effect of α2-adrenoceptors on noradrenaline release. In the first study, GH-releasing factor (GRF)-induced GH release was unaffected in 6 normal volunteers by the prior administration of idazoxan, suggesting that the α2-receptors involved in GH release are not operative at pituitary level. In the second study, 6 normal volunteers performed a bicycle exercise test with and without prior treatment with idazoxan. The exercise-induced GH response (to 13 ±5 mU/l) was significantly augmented by idazoxan (to 20 ±7 mU/l) which contrasts with the current view of GH release being regulated by stimulatory hypothalamic α2-adrenoceptors and suggests that these α2-adrenoceptors are capable of exerting a dual effect on GH release. The exercise-induced increase in plasma noradrenaline (to 1.45 + 0.19 µg/l) and in heart rate (to 142 + 5 beats/min) were also augmented by idazoxan (to 2.24 ±0.23 µg/l and 152 ±6 beats/min). A similar augmentation of the plasma adrenaline response to exercise was also found, whereas the blood glucose, plasma insulin and potassium response to exercise was unaffected by idazoxan. These results suggest that during exercise in man, α2-adrenoceptors exert a tonic inhibitory influence on noradrenaline release which also serves to limit the exercise-induced

ISSN:0028-3835    

DOI:10.1159/000124616

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

A pharmacological approach was used to study the involvement of opioid peptides and dopamine in mediating the suckling-induced release of prolactin in the lactating ewe (10–20 days post partum). To promote reliable and predictable suckling activity lambs were fitted with elasticated masks to prevent sucking for 4.5 h. After a 1-hour control period of frequent blood sampling, ewes were treated (i.v. injections every 5 min) for a further 75 min with either saline vehicle, an opioid antagonist (naloxone; 4.17 mg/5 min), a dopamine antagonist (metoclopramide; 1.25 mg/5 min), a mixture of naloxone + metoclopramide or a dopamine agonist (apomorphine; 6.6 mg/5 min). Blood was withdrawn at 5-min intervals for determination of plasma prolactin and luteinizing hormone (LH) by radioimmunoassay. Plasma LH concentrations (<1 µg/1) were not significantly affected by any of the drug treatments and there was no evidence for an acute fall in LH associated with suckling- or TRH-induced increases in prolactin secretion. Naloxone significantly (p < 0.05) reduced the mean incremental change in prolactin concentration (ΔPRL) in response to suckling (+ 7 ± 18 µg/ml) compared with saline-infused controls (+79 ± 26 µg/ml), an effect which was completely reversed by combined treatment with naloxone and metoclopramide (+146 ± 56 µg/ml). Metoclopramide alone raised basal prolactin levels by 46% (p< 0.01) but did not affect ΔPRL in response to suckling (+115 ± 52 µg/ml). Neither naloxone, metoclopramide nor a combination of the two drugs affected the subsequent prolactin to TRH (10 µg). Apomorphine, however, completely abolished both the suckling- and TRH-induced release of prolactin. These data are consistent with the hypothesis that the suckling-induced release of prolactin in the ewe depends on a reduced activation of dopamine receptors on pituitary lactotrophs which may be the result of a transient inhibition of dopamine release by endogenous op

ISSN:0028-3835    

DOI:10.1159/000124617

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effects of selective agonists and antagonists of opioid receptors on the secretion of corticotrophin releasing factor (CRF) by isolated rat hypothalami in vitro were studied. Morphine (10–8–10–6M) and the µ-opioid receptor agonists, FK33–824CH (10–8–10–6M) and Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (10–8–10–6M), caused dose-related increases in the release of CRF from isolated hypothalami. The K-opioid receptor agonist, U50,488 (10–8–10–6M), was also weakly active in this respect but the δ-opioid receptor agonist, (D-Pen2, D-Pen5)-enkephalin (2 × 10–10–2 × 10–7M), was not. The stimulatory actions of morphine and Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH on CRF release were antagonized by naloxone (10–8M) and by the µ/δ-opioid receptor antagonist, β-funaltrexamine (β-FNA, 10–9M), but not by the µ/δ-opioid receptor antagonist, ICI-154129 (5 × 10–6M). The effects of U50,488 on CRF release were unaffected by either β-FNA or ICI-154129 but were antagonized by high doses of naloxone (10–6M). The results suggest that both µ- and K-opioid receptors are involved in the stimulation of CRF secretion but that

ISSN:0028-3835    

DOI:10.1159/000124618

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Controversy exists regarding the involvement of H1- or H2-receptors in the PRL-releasing activity of histamine (HA). This could be due to differences in the route of administration of HA and histaminergic compounds. Therefore, we studied the effect on PRL secretion of HA and HA-agonists infused intracerebroventricularly (ICV) or systemically (IA) either alone or in combination with HA-antagonists in male rats. HA administered ICV as well as IA stimulated PRL secretion dose dependently. The stimulatory effect of ICV-infused HA was blocked by the H2-receptor antagonist cimetidine (CIM) and mimicked by the H2-receptor agonists 4-methylhistamine (4-MeHA) and dimaprit (DIM). In contrast, the H1-receptor antagonist mepyramine (MEP) enhanced the PRL-releasing effect of HA while the H1-receptor agonist 2-thiazolylethylamine (2-TEA) had no significant effect. The stimulatory effect of IA-infused HA was blocked by the H1-receptor antagonist MEP and mimicked by the H1-receptor agonist 2-TEA, whereas the H2-receptor antagonist CIM enhanced the PRL-stimulatory effect of HA and the H2-receptor agonist DIM was without effect. 4-MeHA stimulated PRL secretion, but this effect was unrelated to stimulation of H2-receptors. The effect of ICV administered HA was unaffected by IA infused antagonists and the effect of IA administered HA was not altered by ICV infused antagonists. HA had no effect on the PRL release from isolated adenohypophyses, and HA did not stimulate PRL secretion in pituitary stalk-sectioned rats following IA infusion. The findings indicate that HA administered ICV exerts its PRL releasing activity via H2-receptors while HA administered IA stimulates PRL secretion via H1-receptors. Furthermore, HA administered ICV may inhibit PRL secretion via H1-receptors and administered IA may inhibit PRL secretion via H2-receptors. The effect of HA whether infused centrally or systemically is exerted at two discrete suprapituitary sites, presumably within the hypothalamus.

ISSN:0028-3835    

DOI:10.1159/000124619

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The present investigation assessed the ability of atrial natriuretic factor (ANF) to affect hypothalamic neuronal excitability. Single neurons in the rostral septal-preoptic area of the female rat brain were recorded extracellularly and tested for responsiveness to iontophoretically applied and/or pressure-ejected ANF. Neurons responsive to ANF were detected in the lateral septal nucleus, the lateral paraolfactory area, the bed nucleus of the anterior commissure, and the medial preoptic area. The majority of neurons influenced by ANF (16 out of 18) exhibited a decrease in spontaneous firing rate during application of the peptide. In some cases, the inhibitory response outlasted the period of ANF application. When both iontophoretic and pressure ejection techniques were used to apply ANF to an individual neuron, the responses were similar. The results indicate that ANF is capable of modulating the membrane excitability of rat forebrain neurons and suggest that the peptide acts as a neuromodulator/neurotransmitter within the central nervous system.

ISSN:0028-3835    

DOI:10.1159/000124620

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Through the combined demonstration of retrograde transport of horseradish peroxidase (HRP) and immuno-cytochemical staining of thyrotropin-releasing hormone (TRH), the TRH neurons that project to the lateral septum were identified. Following the injection of HRP into the lateral septum, retrogradely labelled neurons were detected in the bed nucleus of stria terminalis (BNST), the ventral pallidum, the anterior commissural nucleus, the lateral preoptic nucleus and the perifornical region. Some neurons in the BNST and the perifornical region were found to contain both TRH and HRP. In contrast, no TRH-containing neurons were labelled with HRP in the paraventricular nucleus, the putative thyrotropic area. These data suggest that TRH neurons projecting to the lateral septum were different from those which send fibers to the median eminence.

ISSN:0028-3835    

DOI:10.1159/000124621

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Using immunohistochemical techniques, we have studied the ontogenetic development of growth hormone-releasing factor (GRF) immunoreactive structures in the rat hypothalamus. Frozen sections of rat hypothalami were stained by the avidin-biotin complex (ABC) method using a specific antiserum against rat GRF. Immunoreactive GRF nerve terminals but not perikarya were first detected in rat fetuses on the 20th day of gestation in the external layer of the median eminence (ME). An increased number of immunoreactive nerve terminals in the ME were observed at 1 and 2 days of age. In addition, perikarya containing immunoreactive GRF-like material were observed in the arcuate nucleus (ARC). Rats at 5 days of age showed a further increase in GRF immunoreactive terminals, which now were also present in the internal layer of the ME. In 10- and 20-day-old rats immunoreactive nerve terminals were only moderately increased in the ME. GRF immunoreactive perikarya were observed in the ARC and also in proximity to the ventromedial nucleus. Moreover, GRF containing fibers were seen projecting from the ARC to the ME. Colchicine treatment of postnatal rats reduced immunostaining of the nerve animals in the ME, but did not affect that of the perikarya. These results are consistent with the view that the neural control of growth hormone secretion develops in the rat during late gestation and continues to mature during the early postnatal period.

ISSN:0028-3835    

DOI:10.1159/000124622

出版商:S. Karger AG    

年代:1986

数据来源: Karger