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Biomedical subjects

K Chihara

Publications and source records attributed to K Chihara.

At least 343 records · Page 19Linked to original sources
PubMed1983

Release of vasoactive intestinal polypeptide into the cerebrospinal fluid of the fourth ventricle of the rat: involvement of cholinergic mechanism.

Vasoactive intestinal polypeptide (VIP) is found abundantly in the cerebrospinal fluid (CSF). In order to clarify its source in the brain and the control mechanism of its release, cerebral ventricles of urethane-anesthetized male rats were locally perfused with the artificial CSF at a constant rate of 120 microliters/min by means of a push-pull cannula and immunoreactive VIP was continuously measured in the effluents obtained at 10 min intervals. The perfusion with veratridine, a depolarizing agent, at a rate of 5 x 10(-4) M/min, caused a significant (P less than 0.01) increase in the effluent VIP levels when the tip of a cannula was placed in the fourth ventricle but not when it was in the third or the lateral ventricle. The release of VIP into the fourth ventricle was also significantly (P less than 0.05) enhanced by the perfusion with acetylcholine (ACh) at a dose of 3.66 x 10(-5) to 1.83 x 10(-4) M/min. A simultaneous perfusion of hexamethonium (1.9 x 10(-4) M/min) blocked ACh-induced VIP release. These results indicate that VIP is released into the CSF from the wall of the fourth ventricle by a mechanism possibly involving nicotine-sensitive cholinergic pathways.

Acetylcholine↗
PubMed1983

Human pancreatic growth hormone-releasing factor stimulates release of growth hormone in conscious unrestrained male rabbits.

The effect on GH secretion of GH-releasing factor (GRF), a 44-amino acid peptide recently isolated from a human pancreatic tumor (hpGRF), was examined in conscious male rabbits. During a 6-h period (1030-1630 h) of the control study individual rabbits exhibited pulsatile GH release with a surge at 1030-1200 h, a trough at 1200-1400 h, and a second peak at 1400-1630 h. Intravenous bolus injections of 1 and 10 micrograms hpGRF caused significant and dose-related increases in plasma GH during both the period of the trough (1300 h) and the surge (1530 h), although the GH responses were obviously higher during the latter than the former period. Passive immunization with anti-somatostatin (SRIF) sheep serum resulted in a prompt increase in plasma GH immediately after an injection of the antiserum. When 0.1, 1, and 10 micrograms hpGRF were successively injected iv at 1215, 1345, and 1515 h, respectively, maximum levels of plasma GH after hpGRF in anti-SRIF sheep serum-treated rabbits were significantly higher than in animals given normal sheep serum. The plasma GH responses to 10 micrograms hpGRF, given iv only once at 1515 h in normal sheep serum-treated animals, were not different from those to 10 micrograms hpGRF injected at 1515 h after the prior administration either of the smaller hpGRF dose (0.1 micrograms, 1215 h; 1 microgram, 1345 h), nor of the large dose (10 micrograms, 1100 h). These findings suggest the following: 1) that the secretion of GH is pulsatile in conscious, unrestrained male rabbits; 2) that hpGRF is a potent secretagogue for GH release in rabbits as well as other species; 3) that the magnitude of plasma GH response to hpGRF is different according to timing of the injection during the course of pulsatile GH secretion but is not influenced by the prior administration of hpGRF (no priming effect); and 4) that the responsiveness of plasma GH to hpGRF is affected by circulating endogenous SRIF.

Animals↗
PubMed1983

Unresponsiveness of GH and cortisol to insulin-hypoglycemia in a patient with sub-total pancreatectomy.

Responses of plasma growth hormone (GH) and cortisol to insulin-induced hypoglycemia were repeatedly examined during a therapy of diabetes mellitus in a sub-totally pancreatectomized patient. During a mild control period of diabetes mellitus without any hypoglycemic attacks, insulin-induced hypoglycemia evoked a remarkable increase in plasma GH as well as cortisol while neither GH nor cortisol responded to insulin hypoglycemia during the strict control period with frequent episodes of hypoglycemia. On the other hand, plasma GH and cortisol responses to all other endocrinological stimuli were normal. The mechanism of such impaired hormone secretion during the strict control period of diabetes mellitus in this patient remains unclear.

Glucagon↗
PubMed1982

Central nervous system effect of calcitonin: stimulation of prolactin release in rats.

Effect of [Asu 1,7]eel calcitonin (CT) on prolactin (PRL) release was examined in male rats under urethane anesthesia. Intravenous injection of 4-20 micrograms [Asu1,7]eel CT did not modify plasma PRL levels. Injections of 0.5-2.5 micrograms [Asu1,7]eel CT into the lateral ventricle produce a significant and dose-related increase of plasma PRL within 10 min of injection. When intraventricularly injected in an equimolar dose (0.74 nmol/10 microliters), eel CT11-32, eel CT15-32, [Asu1,7]eel CT1-16 and [Asu1,7]eel CT1-9 showed 44.8, 25.7, 19.9 and 10.1% the potencies of [Asu1,7]eel CT, respectively, in stimulating activity of PRL release. The rise of plasma PRL after [Asu1,7]eel CT injection were significantly less or abolished not only in hypothalamic-lesioned rats but also in rats with complete deafferentation. Pretreatment with alpha-methyl-p-tyrosine (250 mg/kg, 12 h before) but not with p-chlorophenylalanine (300 mg/kg, 72 and 24 h before) resulted in a suppression of [Asu1,7]eel CT-induced PRL release. These results suggest the following: first, PRL release is stimulated by centrally injected [Asu1,7]eel CT, the action site of which may exist in the extrahypothalamic area; second, brain catecholamines may be involved in the mechanism of [Asu1,7]eel CT-evoked PRL release; third, the C-terminal portion of the peptide may play an important role in stimulating PRL release.

Animals↗
PubMed1982

Antagonizing effect of lithium on the development of dopamine supersensitivity in the tuberoinfundibular system.

We investigated whether receptor supersensitivity occurs in the tuberoinfundibular dopaminergic system, as reported in the nigrostriatal and mesolimbic areas. Animals received either haloperidol or saline for 2 weeks. Five days after the last injection of haloperidol, animals pretreated with haloperidol showed a significantly longer lasting inhibition of prolactin (PRL) secretion by apomorphine, compared with the controls. This dopamine receptor supersensitivity was also observed on the 12th, but not the 33rd day after the cessation of haloperidol administration. The effect of lithium on this dopamine supersensitivity in PRL release was investigated. All rats were treated with haloperidol and fed either a diet containing lithium carbonate or a diet without lithium for 2 weeks. Lithium administration with haloperidol resulted in the inhibition of PRL-lowering action of apomorphine at 5 days of withdrawal from haloperidol, indicating that the supersensitivity of dopamine receptors of dopamine receptors on pituitary lactotrophs were decreased by lithium. This action of lithium may be related to the prophylactic effect of the drug on the manic-depressive disease.

Animals↗
PubMed1982

Effect of long term bromocriptine treatment on glucose intolerance in acromegaly.

Blood glucose, plasma GH, insulin and glucagon levels during oral glucose tolerance test before and after treatment with bromocriptine (5-20 mg daily for 2-9 months) were investigated in eleven acromegalic patients with glucose intolerance. Nine out of 11 patients showed improvement or normalization in glucose tolerance after bromocriptine therapy. Basal levels of plasma GH were markedly decreased in 7 of 11 patients treated, although the improved glucose tolerance was not always associated with a drop of basal plasma GH levels. In contrast, basal plasma glucagon level showed a distinct fall in all the patients whose glucose tolerance was improved, but unchanged in whom glucose tolerance was not ameliorated. The mean values of plasma GH and glucagon after oral glucose load were significantly lower during bromocriptine therapy than those before the treatment, respectively. Basal levels of plasma insulin and its response to glucose load did not change after bromocriptine treatment. Bromocriptine thus appears to be a good alternative in the treatment of glucose intolerance in acromegalic patients and the improvement of glucose tolerance by bromocriptine may be related to the reduction in plasma glucagon levels. The possibility, however, is not excluded that a decrease by bromocriptine in the total daily GH secretion is a cause of the improved glucose tolerance.

Acromegaly↗
PubMed1982

Attenuation by hypocalcemia of pulsatile growth hormone secretion in conscious male rats.

The effect of hypocalcemia following parathyroidectomy (PTX) on growth hormone (GH) secretion was investigated in unrestrained, unanesthetized male rats bearing chronically implanted indwelling cannulae. During a 6-hour period, starting at about 10 a.m., control rats with a serum calcium (Ca) value of 8.11 +/- 0.38 mg/dl (mean +/- SEM) 2 weeks after sham-operation showed secretory bursts of GH similar to those observed in conscious intact rats. Under hypocalcemia of 4.88 +/- 0.32 mg/dl 2 weeks after PTX, GH secretory episodes were completely suppressed throughout the study. Plasma prolactin (PRL) levels were also decreased in PTX rats as compared with those of sham-operated rats. Daily food intake and body weight gain as well as serum T4 levels in PTX rats were not different from those of sham-operated and intact rats. Pituitary GH content of PTX rats was significantly lower than that of sham-operated and control rats. Pulsatile GH secretion was partially restored in PTX rats by raising serum Ca to 8.43 +/- 0.27 mg/dl through feeding with high Ca diet containing 7% Ca. Immediately after intravenous injection of antisomatostatin sheep serum, pulsatile GH surges recovered in PTX rats despite hypocalcemia of 4.48 +/- 0.74 mg/dl. The mean plasma 6-hour GH levels were significantly higher than those of normal sheep-serum-treated PTX rats (p less than 0.001). These findings suggest that the episodic release of GH is suppressed in hypocalcemic rats after PTX, at least partially via circulating endogenous somatostatin.

Animals↗
PubMed1982

Effect of vasoactive intestinal polypeptide on growth hormone secretion in perifused acromegalic pituitary adenoma tissues.

The effects of vasoactive intestinal polypeptide (VIP), dopamine, and somatostatin (SRIF) on GH secretion were examined in vitro in perifused pituitary adenoma tissues obtained at surgery from seven patients with acromegaly. The perifusion of VIP at 5 x 10(-8) M resulted in a significant increase in effluent GH levels in five of the seven adenomas. A dose-related GH response was observed from 5 x 10(-9) to 5 x 10(-7) M VIP in two adenomas examined. SRIF at 5 x 10(-8) to 10(-7) M suppressed not only baseline secretion of GH but also inhibited GH rises elicited by VIP in six of the seven adenomas. Dopamine at 5 x 10(-7) to 5 x 10(-6) M decreased the baseline secretion of GH in six of the seven adenomas. In four of the six adenomas responsive to dopamine, dopamine suppressed VIP-induced GH release when perifused simultaneously. In the remaining two dopamine-sensitive adenomas in which VIP alone failed to affect GH release, the inhibition by dopamine of GH release was blocked by VIP perifused concomitantly with dopamine. Synthetic TRH or theophylline perifused at the end of the experiment stimulated GH release in all of the adenomas, indicating the viability of tumor cells throughout the study. These results suggest that VIP stimulates GH release by its direct action on pituitary adenoma cells of acromegalic patients and that VIP, SRIF, and dopamine interact at the pituitary level in modulating GH secretion from these adenomas.

Acromegaly↗
PubMed1982

Tolbutamide stimulates gastric somatostatin release from isolated perfused rat stomach.

The effect of tolbutamide on somatostatin release from the isolated perfused stomach was investigated in both normal and streptozotocin-diabetic rats. Tolbutamide (10, 100, and 1000 microgram/ml) evoked a significant and dose-dependent increase in gastric somatostatin release. The tolbutamide (100 microgram/ml)-induced gastric somatostatin secretion was not influenced by differences in glucose concentration (1.5, 5.5, and 16.5 mM) throughout the perfusion period. Tolbutamide (100 microgram/ml)-induced gastric somatostatin release in streptozotocin-diabetic rats was significantly higher than in normal rats. Thus, tolbutamide is a potent secretagogue for gastric somatostatin secretion, and this effect is more prominent in diabetic animals.

Animals↗
PubMed1981

Inhibition by lithium of dopamine receptors in rat prolactin release.

We investigated the effect of lithium on prolactin (PRL) secretion in both urethane-anesthetized rats and right atrial catheter-bearing conscious rats. Basal plasma PRL levels were not significantly altered for 4 h after lithium administration. However, lithium treatment apparently potentiated PRL release by haloperidol in both conscious and urethane-anesthetized rats. In addition, the inhibition by apomorphine of PRL secretion was significantly antagonized by lithium in conscious rats. Lithium had no effect on the enhancement of PRL secretion by either 5-hydroxytryptophan or beta-endorphin in conscious rats. These observations indicate that lithium affects PRL secretion when dopaminergic neural activity is altered. Therefore, it is possible to postulate that the decrease of dopamine receptor sensitivity by lithium may be related to the therapeutic action of the drug on affective disorders.

5-Hydroxytryptophan↗