Yoshihisa Hashigami

Increased neuropeptide Y concentrations in cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage.

We investigated the possible relation between neuropeptides and cerebral vasoconstriction in samples of ventricular or cisternal cerebrospinal fluid from 14 patients with subarachnoid hemorrhage. Neuropeptide Y, calcitonin gene-related peptide, atrial natriuretic peptide, and pituitary polypeptide 7B2 were present in the cerebrospinal fluid of these patients. Concentrations of calcitonin gene-related peptide and 7B2 were not significantly different from those in control subjects, but that of atrial natriuretic peptide was significantly lower. Although the mean concentration of neuropeptide Y was not significantly higher than control, consecutive determinations showed an increase 6-11 days after the onset of subarachnoid hemorrhage. An initially high 7B2 concentration decreased gradually, although half the patients showed a second increase greater than 10 days after the onset. Considering the well-recognized vasoconstrictive effect of neuropeptide Y, it is possible that this increase in its concentration in the cerebrospinal fluid plays a role in the pathogenesis of the cerebral vasospasm that is often seen after subarachnoid hemorrhage.

Plasma and urine concentrations of atrial natriuretic peptide in patients with diabetes mellitus.

To examine whether plasma and urine concentrations of human atrial natriuretic peptide (hANP) are altered in patients with diabetes mellitus (DM), plasma and urine hANP concentrations were evaluated in 86 patients with diabetes mellitus using an extraction procedure. The mean recovery rate of extraction was 71.8 ± 0.6% (mean ± SEM). The major immunoreactive component of hANP in extracted plasma and urine appeared to be identical to synthetic ahANP as judged by reverse-phase high-performance liquid chromatography (HPLC). The patients were divided into three groups according to their renal complications. The patients in group 1 had no apparent abnormality in serum creatinine, serum or urine P2-microglobulin (P2-MG), or urine N-acetyl-β-D-glucosaminidase (NAG); those in group 2 showed either P2-MG or NAG abnormality but no creatinine abnormality. The patients in group 3 were thought to have an established diabetic nephropathy and showed a serum creatinine increase. Plasma ANP concentrations in groups 1, 2, and 3 were 10.7 ± 2.1, 19.9 ± 5.6, and 39.2 ± 9.9 fmol/ml, respectively. These values in groups 2 and 3 were significantly higher than the control values (p <0.05 or p <0.01 versus 6.2 ± 0.7 fmol/ml). Urine ANP concentrations in group 1 were also within normal range, though those in groups 2 and 3 markedly increased in comparison with normal values. Positive correlations were found between plasma ANP and serum creatinine (r = 0.398, n = 35, p <0.05), serum P2-MG (r = 0.406, n = 45, p <0.01), and urine NAG (r = 0.625, n = 35, p <0.01). These results suggested that ANP might be an early indicator for disturbance in body fluid homeostasis due to diabetic nephropathy, as urine NAG, an early marker for renal tubular damage, best correlated with plasma ANP concentrations.

Pituitary, hypothalamic and pancreatic 7B2 concentrations in rats with streptozotocin-induced diabetes and spontaneously diabetic mice.

The pituitary protein, 7B2 has been demonstrated in the pancreas and is known to be present in very high concentrations in pancreatic endocrine tumors. To investigate whether any changes in 7B2 concentrations might be present in the pancreases affected by different types of diabetes and whether the diabetic state itself might affect pituitary and hypothalamic 7B2 concentrations, streptozotocin (STZ)-treated rats and mice with natural-onset diabetes (obese hyperglycemic, or ob/ob, mice and non-obese diabetic, or NOD, mice) were employed. A significant reduction in pancreatic 7B2 concentrations was found in STZ-treated rats. The pancreatic 7B2 concentration was significantly high in ob/ob mice (p <0.05, versus the concentration in their lean littermates, and the decrease observed in older NOD mice. appeared to parallel their insulin reserve. Pituitary and hypothalamic 7B2 concentrations were similar in STZ-treated and control rats. A reduction in pituitary and hypothalamic 7B2 concentrations was observed in older NOD mice (both p <0.01 versus respective values in younger mice). In ob/ob mice, a significant reduction was also found in hypothalamic 7B2 concentration (p <0.01 versus that in control mice). Gel permeation chromatography showed that 7B2 immunoreactivity comprised two molecular components, and the relative proportion in the pancreas differed from that in other tissues. In the pancreas, a smaller molecular component was predominant (elution coefficient, 0.62). Plasma immunoreactive 7B2 levels were, however, similar in STZ-treated and control rats, and the main immunoreactive component level in plasma was similar to those in the pituitary and hypothalamus. These results may indicate that pancreatic 7B2 concentration varies according to pancreatic insulin concentration, and that the source of circulating 7B2 might not be the pancreas. Pituitary and hypothalamic 7B2 concentrations appeared to be altered in the diabetic state.

ラットの視床下部-下垂体系に対するγ-Oryzanolの影響

The effects of gamma oryzanol (gamma-OZ), a ferulic acid of triterpene alcohol, on the synthesis and release of the growth hormone (GH) and prolactin (PRL) in vitro and turnover rates of hypothalamic catecholamines were investigated. A single subcutaneous injection of 20 mg/kg of gamma-OZ suppressed GH synthesis and PRL release 1 hour after the injection. gamma-OZ increased medial basal hypothalamic (MBH) dopamine (DA) content, and the DA content was decreased by a treatment of alpha-methyl-p-tyrosine (alpha MpT), a tyrosine hydroxylase inhibitor, indicating increased synthesis and release of DA in MBH by gamma-OZ. gamma-OZ did not alter norepinephrine (NE) content in MBH, while the NE content was significantly decreased, indicating unchanged synthesis and increased release of NE in MBH by gamma-OZ. These results may explain the previous data concerning the changes in serum levels of GH and PRL by gamma-OZ and also suggest that gamma-OZ can affect the synthesis and/or release of at least two hypothalamic neurotransmitters, DA and NE, resulting in the alterations of anterior pituitary hormone synthesis and/or release.

実験的甲状腺機能異常ラットにおける血漿, 心房及び視床下部心房性Na利尿ペプチド(ANP)の変動について

In order to assess a possible involvement of thyroid hormone in atrial natriuretic peptide (ANP), experimentally induced hyper- and hypothyroid rats were employed, and the immunoreactive rat ANP (IR-ANP) concentrations in plasma, atria and brain regions including the hypothalamus were measured by a specific radioimmunoassay. Plasma IR-ANP concentration in hypothyroid rats was 14.5 +/- 2.9 (mean +/- SD) fmol/ml, significantly lower than that in control rats (p less than 0.05 vs control of 24.9 +/- 9.7 fmol/ml). Plasma IR-ANP concentration in hyperthyroid rats was 66.4 +/- 9.7 fmol/min, significantly higher than that in the controls (p less than 0.01). Atrial IR-ANP concentration in hyperthyroid rats was significantly lower than that in the controls (79.9 +/- 11.1 nmol/g vs 133.5 +/- 21.2 nmol/g (control), p less than 0.05), though no significant change was observed in atrial IR-ANP concentration in hypothyroid rats. While hypothalamic ANP concentration in hypothyroid rats was significantly lower than that in the controls (17.5 +/- 3.5 pmol/g vs 31.9 +/- 1.9 pmol/g (control), p less than 0.05), there was no significant change of that in the hyperthyroid rats. On reverse phase high performance liquid chromatography, the major peak in plasma and hypothalamus extract was thought to be identical to synthetic alpha-rat ANP (1-28). These results may suggest that in the hyperthyroid state an excessive amount of ANP is released from atria into the blood, and that in the central nervous system thyroid hormone involve ANP metabolism being different from the atrium.