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G B Makara

Publications and source records attributed to G B Makara.

At least 19 recordsLinked to original sources
PubMed1992

Influence of oligopeptide aldehydes on intracellular Ca2+ concentration in rat pituitary cells.

We investigated the effects of some synthetic tripeptide aldehydes, earlier shown to influence pituitary hormone secretion and 45Ca2+ uptake, on the intracellular free Ca2+ concentration ([Ca2+]i) of rat anterior pituitary cells in suspension. Boc-D-Phe-Leu-Phenylalaninal or Boc-D-Phe-Leu-Prolinal in the tested range of 1-100 or 200 microM, respectively, were ineffective in influencing basal [Ca2+]i but caused a concentration-dependent inhibition in K+ (25 mM)-induced [Ca2+]i elevation. The IC50 of both effects was about 50 microM. In contrast, they did not interfere with the stimulation caused by the calcium channel agonist BAY K 8644 and were also ineffective in influencing the receptor-mediated stimulus of thyrotropin-releasing hormone on [Ca2+]i. On the basis of the present and foregoing results the possible involvement of calcium channels is discussed, but different mechanisms mediating the tripeptide aldehyde inhibition are also considered. A third tripeptide aldehyde, Boc-Gln-Leu-Lysinal (Boc-GLL), showed ionophore-like properties. This nontoxic substance caused a dose-dependent rise up to 400% (at 100 microM) in [Ca2+]i. Its effect is not mediated by voltage-dependent calcium channels, as it cannot be inhibited either by the classical calcium channel antagonists verapamil and nifedipine, or by the above-mentioned inhibitory tripeptide aldehydes. When we decreased the extracellular Ca2+ concentration by the addition of 4 mM EGTA, the effect was inverted and Boc-GLL caused a large fall in [Ca2+]i. We suggest that Boc-GLL may open cell membrane pores through which Ca2+ moves along the concentration gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

The relative importance of hypothalamic neurons containing corticotropin-releasing factor or vasopressin in the regulation of adrenocorticotropic hormone secretion.

Corticotropin-releasing factor (CRF-41) and arginine vasopressin (AVP) are the two major factors that regulate adrenocorticotropic hormone (ACTH) secretion. The two neurohormones are co-localized in the parvocellular neurons of the paraventricular nuclei (PVN) of the hypothalamus and are capable of potentiating each others' action on freshly excised anterior pituitary fragments or cells in vitro. Transection of all axons entering the medial basal hypothalamus from anterior and lateral directions blocks ACTH release induced by either adrenalectomy or ether-surgery stress. Adrenalectomy-induced ACTH release is almost completely suppressed by a long-term lesion of the PVN. Stress-induced ACTH release is blocked for only a few days after PVN lesion and the pituitary-adrenal response to ether-surgery stress returns to a large extent by a few weeks after PVN lesioning. This remarkable plasticity can be observed also in the homozygous Brattleboro rat, therefore it is not dependent on mediation by AVP. When parvocellular CRF-41- and AVP-containing cells are present, and the anterior lobe ACTH cells are desensitized to the stimulating effects of AVP, the ACTH response to haemorrhage and immobilization is markedly decreased. This indicates that AVP may partially mediate ACTH release under normal conditions. The hypothalamic control of the pituitary-adrenocortical system has a remarkable degree of redundancy which may compensate, at least under stressful conditions, for disruption of the function of CRF-41-containing cells of the paraventricular nucleus, the major source of CRF-41 in the stalk-median eminence.

Adrenocorticotropic Hormone↗
PubMed1992

Possible mediation of GABA induced growth hormone secretion by increased calcium-flux in neonatal pituitaries.

Gamma-aminobutyric acid (GABA) stimulates growth hormone (GH) secretion from pituitaries of young (less than 20-day old) rats (1,2). Present work revealed that the GH stimulatory effect of GABA was abolished in the absence of calcium and response was attenuated by Nifedipine. The calcium efflux from 45CaCl2 preloaded neonatal pituitaries was enhanced by GABA or by muscimol, and this effect was antagonized by the GABA antagonist picrotoxin. In pituitaries of 21 day old or adult rats GABA stimulated neither GH secretion nor calcium efflux. These results indicate that in neonatal pituitaries GABA influences calcium transport and its GH releasing effect is linked to the presence of calcium.

Animals↗
PubMed1991

Effect of dexamethasone implanted in different brain areas on the morphine-induced PRL, GH and ACTH/corticosterone secretion.

We studied the effect of dexamethasone (DEX) implantation in male Wistar rats to elucidate the site of action of morphine-induced prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH) and corticosterone (B) secretion. DEX or cholesterol was implanted in the close vicinity of the paraventricular (PVN), or the arcuate nuclei (ARN) of the hypothalamus or into the hippocampus. Five days after implantation blood samples were taken 30 min after i.p. morphine by decapitation or through an indwelling cannula 15, 30, 60 min after i.v. injection. DEX implanted near the PVN resulted in a blockade of morphine-induced ACTH and B secretion. In contrast, GH response to morphine was enhanced, while that of PRL was unchanged. DEX implanted near the ARN significantly inhibited the PRL-releasing effect of morphine, but was without any influence on the PRL secretion induced by haloperidol. There was a partial reduction in the B response to morphine, and GH secretion was unchanged. Dorsal hippocampal implants were without any effect on the morphine-induced GH, PRL or B secretion. We suggest that the site of glucocorticoid inhibitory action in the hypothalamus is the PVN for the opiate-induced ACTH/B secretion, and the ARN for the morphine-induced PRL release. The enhanced GH response to morphine observed in DEX-PVN implanted rats might be due to a decreased somatostatin tone.

Adrenocorticotropic Hormone↗
PubMed1991

Prolactin response to morphine in intact and adrenalectomized lactating rats.

To examine the hypothesis that the increased adrenocortical activity during lactation induced the loss of the prolactin (PRL) -releasing effect of morphine, we studied the effect of morphine in adrenalectomized (ADX) and sham-operated primiparous lactating Wistar rats. Animals were adrenalectomized 4 days after delivery. On day 11 of lactation (7 days after ADX), pups were separated from their mother 2 h before morphine or haloperidol injection. Intravenous injection of 5 mg/kg morphine did not change plasma PRL levels in the sham-operated lactating rats, but it resulted in a significant increase of plasma PRL levels in ADX lactating animals, with or without corticosterone replacement. Catalepsy following 10 mg/kg i.v. morphine was also markedly enhanced in ADX lactating animals. The PRL response to 0.5 mg/kg haloperidol was higher in ADX lactating animals than that in the controls. Morphine given 2 h after haloperidol treatment resulted in a further increase of plasma PRL in ADX, but not in the sham-operated lactating animals. These results suggest that adrenal hyperfunction may lead to a loss of sensitivity to morphine during lactation.

Adrenalectomy↗
PubMed1991

Pituitary corticotrophs proliferate temporarily after adrenalectomy.

Relationship of corticotroph proliferation answer and survival time after adrenalectomy was examined. Corticotroph proliferation rates were detected by short-term 3H-thymidine radiolabeling, then ACTH immunostaining and autoradiography. Effect of adrenalectomy on corticotroph proliferation rate was examined in vivo and an elevation was demonstrated first on the second postoperative day, increasing on the third-fourth day postoperatively and then decreasing. Effects of different secretagogues on corticotroph proliferation were examined in short-term pituitary monolayer cultures taken from ADX rats. CRF and Forskolin treatment potentiated corticotroph proliferation in cultures taken from adrenalectomized rats, but not in the controls. We suggest that croticotroph proliferation is stimulated via the cAMP-proteinkinase A pathway, while adrenalectomy plays a permissive role.

Adrenalectomy↗
PubMed1991

Corticotropin-releasing hormone-containing neurons in the hypothalamo-hypophyseal system in rats six weeks after bilateral lesions of the paraventricular nucleus.

Corticotropin-releasing factor-like immunoreactive nerve fibers and varicosities are present in the pituitary stalk and median eminence 6 weeks after bilateral lesioning of the hypothalamic paraventricular nucleus. The total immunoreactivity may reach 10% of the control density. The origin of these fibers was investigated 3 days after hypothalamic transections in paraventricular-lesioned (6 weeks postoperatively) rats. Accumulations of corticotropin-releasing factor immunostaining were observed in the proximal portions of the transected axons and in neuronal perikarya. Fibers with retrograde labeling were seen lateral and dorsolateral from the sagittally oriented knife cuts which transected the retrochiasmatic area and cells were found in the supraoptic nucleus and in the perifornical nucleus (dorsal-dorsolateral to the fornix), ipsilateral to the lesion. No corticotropin-releasing factor immunostained cells were seen in other hypothalamic or preoptic nuclei which project to the median eminence or the posterior pituitary. Corticotropin-releasing factor containing cells in the supraoptic and perifornical nuclei may have an importance in stress response in rats with long-term paraventricular lesions.

Animals↗
PubMed1991

Reevaluation of the role of alpha 2-adrenoreceptors in morphine-stimulated release of growth hormone.

The relationship between opioidergic and alpha 2-adrenergic system in the regulation of GH secretion was studied using a novel alpha 2-antagonist, CH-38083, and chronic treatment with yohimbine or clonidine. In male Wistar rats morphine (3 mg/kg s.c.), and clonidine (31 micrograms/kg i.p.) induced a significant increase in plasma GH levels. The pretreatment with the alpha 2-antagonist yohimbine (1 and 3 mg/kg) effectively inhibited the GH releasing effect or morphine and clonidine. CH-38083 at the dose of 1 mg/kg did not interfere with the morphine-induced GH secretion, while it fully antagonized the GH-releasing effect of clonidine. Higher doses (3 and 5 mg/kg) of CH-38083 only partly inhibited GH secretion induced by morphine. In rats chronically treated with clonidine (2 micrograms/ml in the drinking water for 14 days) the GH response to an injection of clonidine was blocked, while the effect of morphine on the GH secretion remained unchanged. In long-term castrated rats the effect of clonidine (15, 31 and 250 micrograms/kg i.p.) on the GH secretion was significantly blunted, while the GH-releasing effect of morphine (1, 3 and 5 mg/kg s.c.) remained unchanged. The replacement of testosterone (10 mg/kg for 4 days) in castrates restored the effect of clonidine, whereas it decreased the stimulatory action of morphine on the GH secretion. In rats chronically treated with yohimbine (2 mg/kg i.p. 2-3 times daily for 14 days until sacrifice), the GH response to a high dose of clonidine (0.5 mg/kg i.p.) was blocked, while the effect of morphine (5 mg/kg s.c.) was significantly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Anterolateral hypothalamic deafferentation inhibits histamine-induced prolactin secretion and potentiates TRH-induced thyrotropin secretion in male rats.

We studied the effect of histamine on serum prolactin and thyrotropin (TSH) levels in male rats with anterolateral hypothalamic deafferentation of hypothalamic connections or anterolateral cut (ALC). The success of ALC was confirmed by immunohistochemistry of somatostatin (SRIF) in the medial basal hypothalamus. ALC did not affect basal prolactin or TSH levels. Thyrotropin-releasing hormone (TRH, 200 ng/rat, i.p.) did not affect prolactin secretion either in sham-operated or ALC rats. In sham-operated rats intracerebroventricularly administered histamine increased significantly prolactin levels. Hypothalamic deafferentation abolished the effect of histamine on prolactin levels. TRH increased significantly serum TSH levels both in sham-operated controls and ALC rats. In the latter, however, the TSH-secretory response to TRH was significantly (p less than 0.05) larger compared to the controls. Intracerebroventricularly infused histamine (2 micrograms/rat) did not change the TRH-induced TSH secretion in either group of rats. These results show that (1) the effect of histamine on prolactin secretion is mediated through nerve tracts which are destroyed by ALC, and (2) cutting of afferent TRH (through sensitization) and SRIF fibers (through lacking inhibition) entering medial basal hypothalamus may both contribute to the enhanced TSH response to exogenous TRH.

Animals↗
PubMed1991

Inhibition of suckling-induced prolactin release by dexamethasone.

The effect of dexamethasone (DEX) treatment (400 and 200 micrograms/kg BW 21 and 2 h before suckling stimulus, respectively) on suckling- and domperidone (DOMP)-induced PRL release was investigated in freely moving, primiparous lactating rats. DEX completely blocked suckling-induced plasma PRL release without affecting DOMP-induced release of the hormone suggesting a central action of DEX. The effect was transient because it could not be detected on the second day of testing. The effect of DEX implanted in three different brain areas on suckling- and DOMP-induced PRL release was also tested. Implants surrounding the hypothalamic paraventricular nuclei and dorsal hippocampus failed to affect PRL release induced by suckling stimulus. Surprisingly, DEX suppressed PRL release induced by suckling stimulus when it was implanted into the medial basal hypothalamus. These findings demonstrate that DEX is a potent inhibitor of the suckling-induced PRL release. They also indicate that the site of action of DEX is not at the anterior pituitary gland or the paraventricular nuclei and hippocampus because DEX treatment and DEX implants had no effect on plasma PRL levels induced by DOMP and suckling stimulus, respectively. Our data suggest that the effect of DEX is mediated through a region of the medial basal hypothalamus. The observed transient block in suckling-induced PRL release may be physiologically relevant during stress in lactating mothers for conserving pituitary stores of the hormone needed for milk production or being able to adapt to a rapid change in osmoregulation.

Animals↗
PubMed1991

Do the circulating neurohypophysial hormones affect basal or stress induced prolactin (PRL) release in male rats?

The action of acute administration of oxytocin (OXY), vasopressin (AVP) or its analog 1-deamino-8-D-arginine-vasopressin (dDAVP) on basal and stress induced PRL release in normal male rats and the effect of chronic injection of AVP on PRL stress response in AVP deficient rats were studied. The hormones (OXY, 600 ng min-1 per rat; AVP 6, 12 or 24 ng min-1 per rat and dDAVP 24 ng min-1 per rat) were infused to conscious rats via the jugular vein for 10 min and then the rats were immobilized under continuing the infusion for further 20 min. In parallel experiments arterial blood pressure (BP) was measured. OXY and 24 ng min-1 AVP caused high BP elevation of the same magnitude, yet the effect of 12 ng min-1 AVP was significantly lower. Neither OXY, dDAVP, nor 6 and 12 ng min-1 of AVP affected basal or stress stimulated PRL values when compared with saline treated animals. 24 ng min-1 of AVP highly stimulated nonstressed PRL levels and no additional stress effect was observed. Intramuscular injection of 2 micrograms (1 U) of AVP daily for 7 days did not influence the basal values or stress induced PRL response in Brattleboro homogygous rats as compared with vehicle treated controls or heterozygous rats treated with AVP or vehicle. These results show that the infusion of 24 ng min-1 per rat of AVP stimulated PRL release which cannot be explained by the nonspecific effect of high BP. Repeated AVP administration did not modulate either the basal or IMO stress stimulated PRL secretion in rats with or without genetic vasopressin deficiency.

Animals↗
PubMed1990

Oligopeptides interfering with calcium channels inhibit prolactin and growth hormone release by cultured anterior pituitary cells of the rat.

A number of oligopeptides, protected at their N termini and possessing an aldehyde residue at their C terminal amino acids, are able to inhibit 45Ca2+ influx into anterior pituitary cells grown in monolayer culture and depolarized with high extracellular potassium concentration. In addition, the same oligopeptides interfere with hormone release, especially with that produced by lactotrophs. Our findings imply that oligopeptides may represent a new class of calcium channel ligands, and the pituitary cells are sensitive targets for them.

Animals↗
PubMed1990

The effect of systemically and locally administered steroids on VIP-like immunoreactive cells in the paraventricular nucleus of adrenalectomized rats.

Seven days after adrenalectomy (ADX) the number of vasoactive intestinal peptide (VIP)- and corticotropin-releasing factor (CRF)-immunoreactive cells in the parvocellular part of the rat paraventricular nucleus (PVN) increased markedly. Dexamethasone in the drinking water (started immediately after ADX) or its local implantation around the hypothalamic PVN reduced the ADX-induced increase in the number of VIP- and CRF-like immunoreactive neurones. The present results suggest that PVN might be the site at which glucocorticoids inhibit the increase in VIP-positive cells after ADX.

Adrenal Glands↗
PubMed1990

Oxytocinergic neurons in rat hypothalamus. Dexamethasone-reversible increase in their corticotropin-releasing factor-41-like immunoreactivity in response to osmotic stimulation.

Recent results have demonstrated altered corticotropin-releasing factor (CRF)-41 content of the neurointermediate lobe (NIL) of the pituitary gland in response to various manipulations including osmotic stimulation. This study was undertaken to determine whether changes in CRF-41 content of the NIL are accompanied by changes in intensity of CRF-41-like immunoreactivity (CRF-41-LI) of neurosecretory neurones of the hypothalamus in response to osmotic stimulation. Wistar rats of both sexes given either tap water ad libitum, 2% NaCl solution, or access to tap water was limited to 20 min daily, for 7 days. Subsets of rats from each group were adrenalectomized (ADX) or treated with dexamethasone (DEX). Thirty-six hour before perfusion with fixative consisting of buffered formaldehyde and picric acid, animals received 75 micrograms colchicine i.c.v. Forty micrometer thick vibratome sections were stained for CRF-LI, arginine vasopressin (AVP-LI) and oxytocin (OXY-LI) using the avidin-biotin-peroxidase complex method. In response to both types of osmotic stimulation magnocellular neurones of the paraventricular (PVN) and supraoptic nuclei (SON) showed increased CRF-LI, AVP-LI and OXY-LI, while CRF-LI of parvocellular perikarya of the PVN decreased. The enhanced CRF-LI seemed to appear in a subset of magnocellular neurones with OXY-LI but not AVP-LI. Increased staining intensities were also observed in magnocellular neurones in ADX rats challenged osmotically. In contrast, systemic DEX administration, as well as implantation of DEX in the area on the SON, sharply attenuated CRF-LI but not AVP-LI or OXY-LI of magnocellular neurones in osmotically stimulated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1990

Role of hypothalamic factors (growth-hormone-releasing hormone and gamma-aminobutyric acid) in the regulation of growth hormone secretion in the neonatal and adult rat.

N-methyl aspartic acid (NMA) was without effect on the pituitary growth hormone (GH) secretion of adult and neonatal rats in vitro. Administration of NMA resulted in a rapid rise of plasma GH levels in intact but not in arcuate-nucleus-lesioned adult rats, indicating that NMA stimulated GH-releasing hormone (GRH) secretion. In 2-day-old rats, both NMA and gamma-aminobutyric acid (GABA) elevated plasma GH levels in a dose-related fashion; GRH administration was without effect. The elevation of plasma GH levels after NMA injection was reduced by administering an antibody to GRH. These results indicate that GH secretion is partly regulated by endogenous GRH in the newborn rat but that the elevation of plasma GH levels after GABA is not mediated by GRH. The high plasma GH levels seen in the newborn rat may result from the independent action of GABA and GRH but the effect of other factors cannot be excluded either.

Aging↗
PubMed1990

Prolactin response to immobilization stress and hemorrhage: the effect of hypothalamic deafferentations and posterior pituitary denervation.

The roles of posterior and anterolateral connections to the mediobasal hypothalamus (MBH) as well as innervation of the posterior pituitary in the PRL response to immobilization (IMO) and hemorrhage (HEM) were studied by means of surgical isolation, performed 6-9 days before stress exposure. Male rats bearing indwelling tail artery cannulae subjected to 120-min IMO reached peak PRL secretion in 5-20 min. HEM of 25% elicited a significant rise of PRL levels. A posterior cut in the MBH, performed without damaging the serotonergic fibers from the brain stem, attenuated the PRL response to 25% HEM, whereas the PRL elevation due to IMO remained unaffected. An anterolateral cut around the MBH eliminated both the IMO- and HEM-induced stimulation of PRL. Posterior lobe denervation reduced by about 27% the PRL response to IMO and eliminated the response to HEM. These results suggest the following conclusions. The neural structures located posteriorly to the MBH are involved in the transfer of signals triggering PRL secretion due to hypovolemia. Intact anterolateral pathways to the MBH and stalk-median eminence region are essential for the PRL-releasing activity under both stimuli. The posterior lobe may be an important link in the PRL stress response in male rats.

Animals↗
PubMed1989

Lack of the suckling-induced prolactin release in homozygous Brattleboro rats: the vasopressin-neurophysin-glycopeptide precursor may play a role in prolactin release.

Suckling stimulus did not induce significant release of prolactin (PRL) in lactating homozygous Brattleboro rats, whereas it did it in heterozygous animals. Daily treatment of homozygous rats with vasopressin partly restored the PRL response to suckling. Findings suggest that vasopressin-neurophysin-glycopeptide precursor missing in homozygous Brattleboro rats may play a role in suckling-induced PRL release.

Animals↗