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Biomedical subjects

K Chihara

Publications and source records attributed to K Chihara.

At least 325 records · Page 18Linked to original sources
PubMed1985

Administration of antisera to vasoactive intestinal polypeptide and peptide histidine isoleucine attenuates ether-induced prolactin secretion in rats.

The effect of immunoneutralization of endogenous vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI)-like peptides by administration of specific and potent antisera to the respective peptides on ether stress-induced prolactin (PRL) release was examined in male rats bearing an indwelling atrial catheter. Forty-five minutes after an injection of 1 ml of either normal rabbit serum (NRS), anti-VIP serum (AVS), anti-PHI serum (APS) or AVS plus APS, the rat was placed for 1 min in a beaker containing an ether-impregnated cotton ball. Ether exposure caused a prompt and significant increase in plasma PRL in all of the animal groups tested. Pretreatment with either antisera did not affect basal plasma PRL levels, whereas plasma PRL rises after ether exposure were significantly lower in rats pretreated with AVS, APS or AVS plus APS than those with NRS. These results suggest that hypothalamic VIP and PHI-like peptides may be involved, at least in part, in the mechanism by which ether stress stimulates PRL secretion in rats.

Animals↗
PubMed1985

Regional distribution of rat growth hormone releasing factor-like immunoreactivity in rat hypothalamus.

A heterologous RIA for rat GH-releasing factor (rGRF) was established using synthetic rGRF-(1-43)OH for both standard reference and radioiodination with the antiserum produced against human GRF-(1-44) NH2. The regional distribution of rGRF-like immunoreactivity (LI) in rat hypothalamus was examined according to the Palkovits microdissection method and compared with that of somatostatin (SRIF)-LI. Both rGRF- and SRIF-LI contents (mean +/- SE; nanograms per mg protein) were highest in the median eminence (rGRF, 32.28 +/- 11.42; SRIF, 109.9 +/- 19.2) and next most abundant in the arcuate nucleus (rGRF, 3.50 +/- 0.47; SRIF, 12.88 +/- 0.60). Only a small amount of rGRF-LI was found in the ventromedial (1.41 +/- 0.51) and dorsomedial (1.16 +/- 0.15) nuclei and the anterior hypothalamic area (1.29 +/- 0.42), whereas rGRF-LI was not detected in the other nuclei of the hypothalamus. A considerable amount of SRIF-LI was contained in the periventricular, ventromedial, and paraventricular nuclei and the anterior hypothalamic area, in accordance with other reports. Gel filtration chromatography revealed that hypothalamic extracts contained a major peak of rGRF-LI corresponding to rGRF-(1-43)OH and two peaks of SRIF-LI equivalent to SRIF-(1-28) and SRIF-(1-14), respectively. These findings indicate that rGRF-LI is localized in the median eminence and arcuate nucleus in the rat and that rGRF-, SRIF-(1-28)-, and SRIF-(1-14)-LI are present in a 1:2.10:6.29 ratio on a molar basis.

Animals↗
PubMed1985

Inhibitory effect of [Asu1,7]-eel calcitonin on growth hormone-secretion in conscious, freely moving, male rats.

The effect of [Asu1,7]-eel calcitonin (ECT), which is an equipotent analog of eel calcitonin (CT), on GH secretion was investigated in freely moving conscious male rats. Pulsatile GH secretion was completely inhibited by iv injection of ECT (2.5 micrograms/rat). The mean 6-h plasma GH levels, 9.54 +/- 2.34 ng/ml (mean +/- SEM) in ECT-treated rats, were significantly lower than those in saline-treated rats (69.9 +/- 9.4 ng/ml, P less than 0.001). In order to examine the action of ECT on the central nervous system, 25 ng ECT dissolved in 10 microliters saline were injected into the lateral ventricle of conscious male rats. The bursts of GH secretion were completely abolished by this dose of intraventricularly (ivt) injected ECT. The mean 6-h GH levels 5.8 +/- 0.8 ng/ml, were also significantly lower than those in control rats (35.8 +/- 6.6 ng/ml, P less than 0.01). Serum Ca levels did not change after the ivt injection of 25 ng ECT but fell significantly after the iv injection of 2.5 micrograms ECT. In order to clarify the inhibitory mechanism of GH secretion by ECT, the effect of ECT on the release of GH elicited by prostaglandin E1 (PGE1), a well-known GH secretagogue acting directly on the pituitary, was examined in vivo as well as in vitro. Both ivt (2.5, 25, or 250 ng/10 microliters X rat) and iv (2.5 or 25 micrograms/rat) injections of ECT caused a significant and dose-dependent suppression of PGE1-induced GH rises in conscious rats. In contrast, 10(-8) to 10(-7) M ECT failed to affect the baseline secretion of GH and its release by 5 X 10(-6) M PGE1 from rat anterior pituitary tissues perifused in vitro. These findings suggest that ECT suppresses GH secretion in the rat, at least in part, through the central nervous system.

Alprostadil↗
PubMed1985

Effect of passive immunization with antisera to vasoactive intestinal polypeptide and peptide histidine isoleucine amide on 5-hydroxy-L-tryptophan-induced prolactin release in rats.

The present study was aimed to clarify, by use of the passive immunization method, the involvement of endogenous vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine amide (PHI)-like peptides in the stimulation of PRL-like immunoreactive material release induced by 5-hydroxy-L-tryptophan (5HTP), a serotonin precursor. We used conscious, freely moving male rats of the Wistar strain (BW, 250-300 g) chronically cannulated with atrial catheters. Anti-VIP serum (AVS) and anti-PHI serum (APS), each generated in rabbits against synthetic porcine VIP and natural porcine PHI, respectively, were highly potent [maximum binding capacity (Bmax): AVS, 55.5 nmol/ml; APS, 5.53 nmol/ml] and specific. Bolus injection of 5HTP (10 mg/kg BW) through the catheter caused a significant increase in plasma PRL (nanograms per ml) in rats pretreated with normal rabbit serum (NRS) [14.3 +/- (SE) 3.8----56.3 +/- 11.2], with AVS (12.3 +/- 3.5----48.5 +/- 6.2), with APS (10.5 +/- 3.9----43.5 +/- 8.8), and with AVS plus APS (9.0 +/- 1.4----28.5 +/- 2.7). The basal PRL concentrations did not differ significantly among these groups, whereas the PRL responses to 5HTP were significantly blunted in AVS plus APS-pretreated rats (P less than 0.05 vs. NRS). To eliminate the modification by dopaminergic control of 5HTP-induced PRL release, the next experiment was performed in rats repeatedly injected with sulpiride, a dopamine receptor antagonist (5 mg/kg BW), every 30 min. The first injection of sulpiride caused a prompt and marked increase in plasma PRL, followed by decreasing but still high levels of plasma PRL upon the subsequent injections of sulpiride every 30 min. The cumulative release area of PRL after pretreatment with AVS plus APS or APS alone was significantly lower than that after NRS (P less than 0.05). The same dose of 5HTP resulted in a significant further increase in plasma PRL exceeding the levels elevated by sulpiride injections in NRS-treated rats. Prior simultaneous administration of AVS and APS resulted in a complete suppression of 5HTP-induced PRL release, whereas pretreatment with either AVS or APS showed only a minimal effect. These results suggest that endogenous VIP and PHI-like peptides are PRL-releasing factors, involved at least in the mechanism of 5HTP-induced PRL release, in which the dopaminergic control may be also involved.

5-Hydroxytryptophan↗
PubMed1985

Idiopathic growth hormone (GH) deficiency, and GH deficiency secondary to hypothalamic germinoma: effect of single and repeated administration of human GH-releasing factor (hGRF) on plasma GH level and endogenous hGRF-like immunoreactivity level in cerebrospinal fluid.

Plasma GH responses to iv administered synthetic human GH-releasing factor-(1-44)-NH2 (hGRF) and the concentration of endogenous hGRF-like immunoreactivity (hGRF-LI) in the cerebrospinal fluid (CSF) were examined in 16 children with GH deficiency (GHD). Ten patients had idiopathic GHD, and six had GHD secondary to germinoma. An iv bolus hGRF (1 microgram/kg BW) injection test was performed the day before and the day after treatment, with a daily 1-h iv infusion of hGRF (2 micrograms/kg BW) for 3 days. Plasma GH increases (greater than 5 ng/ml) after the first iv bolus injection of hGRF occurred in 2 of the 10 idiopathic GHD children and in 4 of the 6 GHD patients with germinoma whereas the first bolus hGRF injection failed to elicit GH release in the remaining 10 patients. The mean +/- SEM peak plasma GH level after the first bolus hGRF dose in the patients with germinoma (8.2 +/- 2.2 ng/ml) was significantly higher than that in the idiopathic GHD patients (2.9 +/- 0.9 ng/ml; P less than 0.05), but significantly lower than that in normal children with short stature (18.5 +/- 2.5 ng/ml; P less than 0.05). In the 2 patients with germinoma and in 5 of the 8 idiopathic GHD children who did not respond to the first hGRF bolus dose, a significant plasma GH response to hGRF occurred during a daily iv infusion of hGRF for 3 consecutive days, whereas the remaining 3 idiopathic GHD children failed to respond to the daily hGRF infusions. The plasma GH response after the second hGRF bolus dose given after treatment with daily hGRF infusions for 3 days was not different from that after the first hGRF bolus in patients with germinoma or that in the idiopathic GHD children. hGRF-LI was not detected (less than 5.8 pg/ml) in the CSF in any of 5 patients with germinoma, whereas it was present in 5 idiopathic GHD patients (mean, 17.5 +/- 0.9 pg/ml), 3 of whom were nonresponders to daily hGRF infusions. From these results, GHD secondary to destruction of hypothalamic GRF neurons might be defined by the following findings: 1) lack of a GH response to the standard provocative tests acting through the hypothalamus; 2) significant increase in plasma GH after a single bolus and/or repetitive iv administration of hGRF; and 3) undetectable or extremely low levels of endogenous hGRF-LI in the CSF. Most of the idiopathic GHD patients responded to the repetitive hGRF infusion, suggesting insufficient secretion of hypothalamic hGRF as the primary defect. However, since hGRF-LI was detectable in the CSF in some of the idiopathic GHD patients, its pathogenesis must be multifactorial.

Adolescent↗
PubMed1985

Presence of growth hormone-releasing factor-like immunoreactivity in human cerebrospinal fluid.

Immunoreactive human growth hormone-releasing factor (I-hGRF) in human cerebrospinal fluid (CSF) was measured by radioimmunoassay using antiserum specific to the C-terminal portion of hGRF(1-44)NH2. Dilution curves of I-hGRF in the CSF were completely parallel to that of synthetic hGRF(1-44)NH2 standard. On Sephadex G-50 column chromatography a single peak of I-hGRF in the CSF was eluted at the position of synthetic hGRF(1-44)NH2. I-hGRF was present in the CSF of all control patients without any endocrine disease (mean +/- SE, 29.3 +/- 2.0 pg/ml) whereas I-hGRF in the CSF was not detectable (less than 5.8 pg/ml) in any of the patients with hypothalamic germinoma. In all patients with idiopathic GH deficiency, I-hGRF in the CSF was measurable but its concentration (15.1 +/- 1.0 pg/ml) was significantly (p less than 0.05) lower than that in the control subjects. No difference in I-hGRF levels of the CSF was observed between patients with acromegaly and control subjects. These findings demonstrate for the first time that I-hGRF is present in human CSF. Measurement of I-hGRF in the CSF may be useful for understanding the pathophysiology of hypothalamo-pituitary diseases.

Acromegaly↗
PubMed1985

Augmentation by propranolol of growth hormone-releasing hormone-(1-44)-NH2-induced growth hormone release in normal short and normal children.

The effect of a 90-min iv infusion of propranolol, a beta-adrenergic antagonist (0.2 mg/kg BW), on basal plasma GH levels and the GH responses to an iv bolus injection of GH-releasing hormone-(1-44)-NH2 (GHRH; 1 microgram/kg BW) was examined in 10 prepubertal children (6 short but otherwise normal and 4 normal). The iv injection of GHRH resulted in significant increases in plasma GH, comparable to those after either insulin-induced hypoglycemia or arginine infusion. Only a small and inconsistent increase in plasma GH levels occurred during the iv infusion of propranolol, whereas simultaneous administration of propranolol with GHRH caused marked enhancement of GHRH-induced GH release in all subjects. The difference between the plasma GH response to GHRH given with propranolol and the response to GHRH given with 0.9% saline was significantly greater than that between the plasma GH level after propranolol and that after 0.9% saline infusion without GHRH injections. There was no difference in plasma GH responses to GHRH, propranolol, or both in the normal short children or normal children. These findings indicate that beta-adrenergic blockade potentiates GHRH-induced GH secretion in prepubertal children.

Child↗
PubMed1985

Effect of [Asu1,7]eel calcitonin on prolactin release in normal subjects and patients with prolactinoma.

The effect of [Asu1,7]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 microgram/kg body weight . h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 micrograms at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 +/- 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 +/- 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 +/- 3.1 vs 33.5 +/- 9.6 ng/ml, P less than 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0-4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10(-9) - 10(-6)M) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.

Adenoma↗
PubMed1985

Lack of plasma prolactin response to intravenously injected vasoactive intestinal polypeptide in patients with prolactin-secreting adenoma.

The effect of an iv bolus injection of 1 microgram/kg body weight of vasoactive intestinal polypeptide (VIP) on plasma prolactin (Prl) levels was tested in 13 normal volunteers and 15 patients with hyperprolactinaemia of various aetiology: 9 with Prl-producing pituitary tumours (6 prolactinoma, 3 mixed pituitary adenoma, secreting Prl and growth hormone (GH)), 6 with hyperprolactinaemia secondary to a hypothalamic lesion (4 craniopharyngioma, 1 hypothalamic germinoma, 1 meningoencephalitis). In the normal subjects, an iv injection of VIP caused a prompt increase in plasma Prl with peaks 2- to 3-fold greater than the basal values. On the other hand, none of the 9 patients with a Prl producing pituitary tumour showed any obvious Prl rise after VIP irrespective of a marked difference in their basal Prl levels. Lack of a Prl response to VIP was also found in the 2 patients with hypothalamic lesions (1 craniopharyngioma, 1 hypothalamic germinoma) whose basal Prl concentration was higher than 100 ng/ml. However, in the remaining 4 patients with hypothalamic lesions whose basal Prl concentration was less than 100 ng/ml, VIP injection resulted in a stimulation of the Prl secretion with a maximal net increment of 11.3 +/- 3.8 ng/ml, which is not different statistically form that (16.3 +/- 3.3 ng/ml) in the normal subjects, but significantly higher than that (-2.3 +/- 2.7 ng/ml) in the 4 patients with Prl-secreting adenoma and a basal Prl concentration of less than 100 ng/ml. These results indicate that the VIP test may be a useful diagnostic tool for discriminating a Prl-producing tumour from a hypothalamic lesion in patients with mild hyperprolactinaemia.

Adenoma↗
PubMed1985

Effect of various catecholamine antagonists on prolactin secretion in conscious male rabbits.

To clarify physiological roles of catecholaminergic systems in the control of rabbit prolactin (PRL) release, the effect of various catecholamine receptor antagonists on plasma PRL levels was examined in conscious, freely moving male rabbits. An intravenous (iv) injection of yohimbin (2.5 mg/kg body wt), an alpha 2-adrenoreceptor antagonist, but not prazosin (2 mg/kg body wt), an alpha 1-adrenergic receptor antagonist, resulted in a significant elevation of plasma PRL. Conversely, propranolol (2.5 mg/kg body wt, iv), a nonselective beta-adrenoreceptor antagonist, and metoprolol (2.6 mg/kg body wt, iv), a beta 1-adrenergic antagonist, slightly but significantly suppressed basal levels of plasma PRL. On the other hand, haloperidol (0.5 mg/kg body wt, iv), pimozide (0.3 mg/kg body wt, iv), sulpiride (5 mg/kg body wt, iv), chlorpromazine (3 mg/kg body wt, iv), and YM-09151-2 (0.2 mg/kg body wt, iv), all dopamine receptor antagonists caused a significant increase in plasma PRL. These results suggest that dopaminergic and alpha 2-adrenergic mechanisms exert a tonic inhibitory role and beta-adrenergic mechanisms, probably beta 1, a tonic stimulatory role in the regulation of PRL release in the rabbit.

Animals↗
PubMed1984

Stimulatory effect of peptide histidine isoleucine amide 1-27 on prolactin release in the rat.

Intravenous injection of pure peptide histidine isoleucine amide 1-27 (PHI) resulted in a prompt and significant increase of plasma prolactin (PRL) in conscious freely-moving male rats. Using a perifusion system of rat anterior pituitary tissues in vitro, effluent PRL levels were also increased by 10(-8)-10(-7) M PHI. A PRL releasing potency of PHI was almost similar with that of vasoactive intestinal polypeptide (VIP) or TRH both in vivo and in vitro. Coupled with the recent immunocytochemical studies showing the dense network of PHI immunoreactive fibers around the hypophysial portal vessels, PHI might be another candidate for PRL releasing factor.

Animals↗
PubMed1984

Noradrenergic modulation of human pancreatic growth hormone-releasing factor (hpGHRF1-44)-induced growth hormone release in conscious male rabbits: involvement of endogenous somatostatin.

To clarify the role of noradrenergic neurons in the regulation of GH secretion, the effects of iv administered noradrenergic antagonists were investigated in freely moving, conscious male rabbits. During a 6-h observation period (1030-1630 h), control rabbits manifested pulsatile GH secretion with surges between 1030-1200 and 1415-1630 h. Phenoxybenzamine, (POB), an alpha-adrenergic blocker (5 mg/kg, twice), abolished the episodic GH surges; propranolol, a beta-adrenergic blocker (2.5 mg/kg, twice), did not. The bolus injection (1 or 10 micrograms) of synthetic human pancreatic GH-releasing factor (hpGHRF) with 44 amino acid residues (hpGHRF1-44) resulted in significant rises in the plasma GH of control animals. The plasma GH responses to hpGHRF1-44 were significantly larger in propranolol-treated than control rabbits. In contrast, POB completely suppressed the hpGHRF1-44-induced GH release. The injection of antisomatostatin (SRIF) serum into POB-treated rabbits did not yield a disinhibition of the episodic GH surges but restored the plasma GH rises after hpGHRF1-44 injection. These results indicate that noradrenaline++ plays an important role in regulating GH secretion in the rabbit. We propose that alpha-noradrenergic blockade suppresses GH release not only by inhibiting the release of hypothalamic GHRF but also by stimulating the secretion of SRIF and that beta-noradrenergic blockade enhances GH release by inhibiting the release of SRIF from the hypothalamus.

Animals↗
PubMed1984

Stimulation of growth hormone by vasoactive intestinal polypeptide in acromegaly.

Vasoactive intestinal polypeptide (VIP) was administered as an iv bolus of 1 micrograms/kg BW to 8 acromegalic patients and in doses of 0.5 and 1 microgram/kg BW to 15 normal volunteers. Both systolic and diastolic blood pressures decreased, and pulse rate increased transiently after VIP injection. VIP stimulated PRL release from the anterior pituitary in normal subjects. Plasma PRL responses to VIP in women were dose dependent and larger than those in men. On the other hand, plasma GH levels rose markedly after VIP injection in all 6 patients with untreated acromegaly. In 2 patients studied after transsphenoidal microadenomectomy, there was no plasma GH response to VIP. In 2 other patients with inactive acromegaly as well as in normal subjects, VIP failed to affect plasma GH levels. In all 6 patients with active acromegaly, LRH (1-2 micrograms/kg BW, iv) did not increase plasma GH levels, but TRH (5-10 micrograms/kg BW, iv) caused significant increases in plasma GH, the magnitude of which was not similar to that of increases seen after VIP injection. Paradoxical GH responses to TRH were not observed in patients in the inactive phase after transsphenoidal surgery. These findings suggest that VIP stimulates GH release in vivo in acromegalic patients. A VIP test as well as a TRH test offer promise as simple and reliable techniques to evaluate the activity of acromegaly, particularly after transsphenoidal surgery.

Acromegaly↗
PubMed1984

Prolactin secretion from human prolactinomas perifused in vitro: effect of TRH, prostaglandin E1, theophylline, dopamine and dopamine receptor blockers.

To clarify the functional characteristics of prolactin (Prl)-producing adenoma cells, the effect of TRH, prostaglandin E1 (PGE1), theophylline, dopamine and dopaminergic antagonists on Prl secretion was examined in vitro in perifused pituitary adenoma tissues obtained at surgery from 8 patients with prolactinoma. Perifusion with TRH at a concentration of 10(-6) to 10(-5) M resulted in a significant increase in effluent Prl levels in 3 of the 8 adenoma tissues. In the remaining 5 adenomas, TRH produced no effect on Prl release in vitro. On the other hand, PGE1 (10(-5) M) stimulated Prl secretion in 2 of the 4 adenomas examined. Addition of theophylline (5.5 mM) caused a marked increase of effluent Prl levels in all 8 prolactinomas regardless of the reactivity to TRH or PGE1. Dopamine (5 X 10(-7) M) suppressed Prl secretion from adenoma tissue in 5 of 7 patients tested but had no effect in the remaining two adenomas. When perifused simultaneously with dopamine, sulpiride (D2-selective dopamine receptor blocker, 5 X 10(-7) M) blocked the inhibitory effect of dopamine on Prl release in 3 of the 4 dopamine-sensitive prolactinomas. In one adenoma responsive to dopamine but resistant to sulpiride, YM-09151-2 (relatively specific D1-dopamine receptor blocker, 5 X 10(-7) M) antagonized the dopaminergic inhibition of Prl release. When perifused alone, neither sulpiride nor YM-09151-2 affected Prl release from any of the adenoma tissues tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗