Tokihisa Kimura

Central Effects of Interleukin-1 on Blood Pressure, Thermogenesis, and the Release of Vasopressin, ACTH, and Atrial Natriuretic Peptide

To assess the central role of interleukin 1-beta (IL-1 beta) in the release of ACTH, vasopressin (AVP) and atrial natriuretic peptide (ANP) and in the regulation of blood pressure and thermogenesis, 3 ng (0.173 pM) x 100-1 x BW-1 (LIL), 30 ng (1.73 pM) x 100g-1 x BW-1 (MIL), and 150 ng (8.63 pM) x 100g-1 x BW-1 (HIL) of human IL-1 beta dissolved in sterile saline were injected intracerebroventricularly to conscious rats. In the control rats, saline alone (5 microliters) was administered. In three other groups, rats were pretreated with indomethacin, a cyclooxygenase inhibitor, given i.v. (1 mg x 100g-1 x BW-1); medium and high doses of IL-1 beta or its vehicle were given. In the LIL group, IL-1 beta increased blood pressure, body temperature and plasma AVP and ANP without any changes in heart rate (HR) and plasma ACTH. In the MIL group, plasma ACTH was increased, and changes in the other parameters were similar to those in the LIL group. In the HIL group, however, the pressor and thermogenetic responses were attenuated; plasma AVP, ACTH, and ANP were increased; and HR was unchanged. In the control (CON) group, none of these parameters was changed throughout the studies. Indomethacin abolished the AVP and ACTH responses to IL-1 beta, but potentiated the pressor and hypothermic responses and increased plasma ANP. These data suggest that the actions of IL-1 beta on AVP and ACTH release and thermogenesis, but not on blood pressure and the release of ANP, are modulated by the stimulated central production of prostaglandins.

The role of GABA in the central regulation of AVP and ANP release and blood pressure due to angiotensin and carbachol, and central GABA release due to blood pressure changes

To assess whether GABA given intracerebroventricularly (i.c.v.) affects vasopressin (AVP) and atrial natriuretic peptide (ANP) release and changes in blood pressure in response to i.c.v. angiotensin (AT II) and carbachol (CB), or whether changes in blood pressure affect GABA release in the brain, experiments were carried out. In experiment I (Ex I), GABA (100 micrograms) with AT II (50 ng) or CB (25 ng) was i.c.v. administered in conscious rats (n = 12). The same dose of AT II or CB alone also was administered without GABA (n = 12). In experiment II (Ex II), AT II (100 ng/kg per min) or nitropuruside (NP, 10 micrograms/kg per min) was intravenously (i.v.) infused and GABA release in the area adjacent to the paraventricular nucleus was determined, using the microdialysis method, in conscious rats (n = 12). In the experiments, mean arterial blood pressure (MABP), heart rate (HR), plasma AVP and/or ANP and plasma Na+ and K+ levels were measured. In Ex I, i.c.v. AT II increased plasma AVP and MABP without changes in HR and plasma ANP, but i.c.v. GABA never affected these responses. Icv CB also increased plasma AVP and MABP with decreased HR, but did not affect plasma ANP. Icv GABA abolished bradycardiac responses, but did not affect the others. In Ex II, the pressor response to i.v. AT II increased GABA release without apparent decreases in plasma AVP. However, the depressor response to NP produced decreases in GABA release with increased plasma AVP. These results shows that i.c.v. GABA did not affect AVP and pressor responses to i.c.v. AT II and CB, but changes in blood pressure modulates GABA release in the brain with changes in plasma AVP.

Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay.

SummaryThe production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.

The roles of GABA in the central regulation of AVP and ANP release and blood pressure in hypertonic saline infusion and hemorrhage

In order to assess the central effects of gamma-aminobutyric acid (GABA) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular function, the following two experiments (Exp) were carried out in conscious rats (n = 24). Experiment I: GABA (10 micrograms/kg.min) was intracerebroventricularly (i.c.v.) administered into conscious rats receiving an intravenous (i.v.) infusion of 2.5 M NaCl, and the vehicle alone was i.c.v. administered under i.v. 2.5 M NaCl in the control group. Experiment II: GABA (12 micrograms/kg.min) was infused i.c.v. in conscious rats during hemorrhage (1.6% of BW) and the vehicle alone was i.c.v. administered during hemorrhage in the control study. In Experiment I, plasma AVP and ANP and mean arterial blood pressure (MABP) increased in response to 2.5 M NaCl, but heart rate (HR) slightly decreased. I.C.V. GABA attenuated the AVP and ANP responses, but did not affect MABP and HR. In Experiment II, plasma AVP increased due to decreases in MABP induced by hemorrhage, but plasma ANP and HR never changed. I.C.V. GABA did not affect plasma AVP and ANP, MABP and HR. These results show that i.c.v. GABA has an inhibitory effect on AVP and ANP release in response to hypertonic NaCl, but not to hemorrhage, but never affected hypertonic NaCl-induced increases in blood pressure.