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S Shiono

Publications and source records attributed to S Shiono.

87 records · Page 5Linked to original sources
PubMed1986

Acetylcholine receptor: characterization of the voltage-dependent regulatory (inhibitory) site for acetylcholine in membrane vesicles from Torpedo californica electroplax.

Evidence for a voltage-dependent regulatory (inhibitory) site on the nicotinic acetylcholine receptor to which acetylcholine binds was obtained in membrane vesicles prepared from the Torpedo californica electric organ. Two rate coefficients, JA and alpha, which pertain to the receptor-controlled ion flux, were measured. A 1000-fold concentration range of acetylcholine was used in a transmembrane voltage (Vm) range from 0 to -48 mV under a voltage-clamped condition at pH 7.4, 1 degrees C. The following observations were made. (i) At low acetylcholine concentrations, the value of JA, the rate coefficient for ion translocation by the active (nondesensitized) state of the receptor, increased with increasing concentration. (ii) JA decreased at high acetylcholine concentrations. (iii) In contrast, alpha, the rate coefficient for receptor desensitization, did not show such a decrease. (iv) When the transmembrane potential of the vesicle membrane was changed to more negative values, the value of KR (the dissociation constant for binding of acetylcholine to the regulatory site) decreased by a factor of approximately 9 for a 25 mV change in Vm, while KI (the dissociation constant for binding of acetylcholine to the receptor site that controls channel opening) did not show such a change and has a value of 80 microM. When Vm is -48 mV, KR has a value of 8 microM. (v) The effect of a transmembrane voltage on the regulatory site was reversible and occurred within the time resolution (5 ms) of the quench-flow technique used in the measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

Nature of atrial natriuretic polypeptide in rat brain.

Using reverse phase high performance liquid chromatography (RP-HPLC) coupled with two radioimmunoassays for atrial natriuretic polypeptide (ANP) with different specificities, we investigated the nature of alpha-rat ANP-like immunoreactivity (alpha-rANP-LI) with a low molecular weight in the rat brain. Two major peaks with alpha-rANP-LI in the extract from rat whole brains were eluted in the vicinity of the elution position of synthetic alpha-rANP, a 28-amino acid polypeptide. These two components co-migrated with synthetic alpha-rANP (4-28) and alpha-rANP (5-28), respectively. The peak corresponding to alpha-rANP (4-28) was the highest, and only a little alpha-rANP-LI was detected at the elution position of alpha-rANP. An identical profile in RP-HPLC was also observed in the extract from the rat hypothalamus. These results indicate that the major components of alpha-rANP-LI with a low molecular weight in the rat brain are alpha-rANP (4-28) and alpha-rANP (5-28).

Animals↗
PubMed1986

The lung as a possible target organ for atrial natriuretic polypeptide secreted from the heart.

Using a specific radioimmunoassay (RIA) for alpha-rat atrial natriuretic polypeptide (alpha-rANP), we have demonstrated the presence of a considerable amount (6.10 +/- 0.38 ng/g) (mean +/- SE) of alpha-rANP-like immunoreactivity (alpha-rANP-LI) in the rat lung, the first organ through which atrial natriuretic polypeptide (ANP) released from the heart passes. High performance gel permeation chromatography coupled with the RIA revealed that most of alpha-rANP-LI eluted at the position of a low molecular weight form corresponding to synthetic alpha-rANP. In 2- or 5-day water-deprived rats, the concentration and content of alpha-rANP-LI in the lung decreased significantly compared with those of control rats. In addition, water-deprivation induced a significant decrease in the plasma concentration of alpha-rANP-LI simultaneously determined. There was a significant positive correlation between the concentrations of alpha-rANP-LI in the lung and plasma (r = 0.591, P less than 0.01). These results indicate the presence of ANP in the lung and suggest physiological roles of ANP in pulmonary function.

Animals↗
PubMed1986

The pharmacokinetics of alpha-human atrial natriuretic polypeptide in healthy subjects.

We have analysed the pharmacokinetics of alpha-human atrial natriuretic polypeptide (alpha-hANP) in healthy subjects, using a two-compartment open model following bolus intravenous injection. The plasma half-times for the fast and slow components were 1.7 +/- 0.07 min and 13.3 +/- 1.69 min respectively. V1 (the volume of the central compartment), VZ (volume of distribution) and VSS (volume of distribution at steady-state) were 5370 +/- 855 ml (89.5 +/- 14.3 ml X kg-1), 32000 +/- 4620 ml (533 +/- 77.0 ml X kg-1), and 11900 +/- 1530 ml (198 +/- 25.5 ml X kg-1) respectively. The mean plasma clearance was 1520 +/- 121 ml X min-1 (25.4 +/- 2.0 ml X min-1 X kg-1.

Adult↗
PubMed1986

Thyrotropin-releasing hormone stimulation of thyrotropin secretion is suppressed by calcium ion antagonists that block transmembrane influx and intracellular mobilization of calcium ion in human subjects.

To evaluate whether extracellular and intracellular calcium ion may be involved in the regulation of TSH secretion in response to TRH in human subjects, the TSH blood level was determined in normal man before and after administration of two kinds of calcium ion antagonists, nifedipine that blocks transmembrane influx of calcium ion and nicorandil that inhibits mobilization of intracellular calcium ion. Administration of nifedipine and nicorandil significantly decreased the blood level of TSH stimulated by TRH, although calcium ion antagonists did not affect the basal level of TSH. The blood level of neither T4, T3, free T4, free T3, nor reverse T3 was altered by administration of calcium ion antagonists. The present study indicates that cytoplasmic calcium ion derived from the extracellular and intracellular sources plays a pivotal role in the controlling of TRH-stimulated TSH secretion in human subjects.

Adult↗
PubMed1986

Central action of atrial natriuretic polypeptide on blood pressure in conscious rats.

The effect of intracerebroventricular administration of atrial natriuretic polypeptide on blood pressure was studied in conscious, unrestrained rats. The intracerebroventricular injection of alpha-human atrial natriuretic polypeptide did not promote any significant change in basal blood pressure, whereas it attenuated central angiotensin II-induced pressor response in a dose-dependent manner. The plasma atrial natriuretic polypeptide level did not change after the central administration of alpha-human atrial natriuretic polypeptide. These data implicate atrial natriuretic polypeptide as a factor in blood pressure regulation in the central nervous system.

Angiotensin II↗
PubMed1986

Centrally infused atrial natriuretic polypeptide attenuates exaggerated salt appetite in spontaneously hypertensive rats.

We have previously shown that atrial natriuretic polypeptide is present in the brain with the highest concentration in the hypothalamus and septum and that intracerebroventricular injection of atrial natriuretic polypeptide inhibits water drinking induced by centrally injected angiotensin II or 24-hour water deprivation in rats. To study further the role of brain atrial natriuretic polypeptide in the control of water and electrolyte balance, the effect of chronic intracerebroventricular infusion of atrial natriuretic polypeptide on salt appetite in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was examined with a free-choice, two-bottle preference test. The intracerebroventricular infusion of 100 ng/hour and 500 ng/hour of alpha-human atrial natriuretic polypeptide preferentially suppressed the intake of 0.30 M NaCl solution and attenuated the elevated preference for the hypertonic saline in spontaneously hypertensive rats while centrally infused alpha-human atrial natriuretic polypeptide had no significant effects on drinking behavior in Wistar-Kyoto rats. Blood pressure did not change significantly throughout the experiment in either rat strain. It is concluded that the exaggerated salt appetite in spontaneously hypertensive rats is blunted by centrally administered atrial natriuretic polypeptide. Such an effect of atrial natriuretic polypeptide along with its antidipsogenic effect suggests that brain atrial natriuretic polypeptide plays a role in water and electrolyte homeostasis and in blood pressure control.

Animals↗
PubMed1986

Increased tissue level of atrial natriuretic polypeptide in the hypothalamus and septum of spontaneously hypertensive rats.

To elucidate the pathophysiological role of atrial natriuretic polypeptide (ANP) in the brain in hypertension, the tissue concentrations and contents of alpha-rat ANP-like immunoreactivity (alpha-rANP-Ll) in the hypothalamus and septum of 4-week or 18-week-old spontaneously hypertensive rats (SHR) were studied using a radio-immunoassay (RIA) for alpha-rANP and compared with those of age-matched Wistar-Kyoto rats (WKY). The concentration and content of alpha-rANP-Ll in these regions of both 4-week and 18-week-old SHR were significantly higher that those of WKY (P less than 0.05). High performance gel permeation chromatography coupled with the RIA showed that the gel filtration profile of alpha-rANP-Ll in SHR was essentially identical to that of WKY. Since the hypothalamus and septum are known to be critical areas for water and electrolyte balance, and blood pressure control, these results suggest that ANP plays a pathophysiological role in these brain regions of SHR.

Animals↗
PubMed1986

Atrial natriuretic polypeptide in the brain: implication of central cardiovascular control.

Biologically active peptides isolated from peripheral organs often occur in the central nervous system, and vice versa. There is evidence that the effects of centrally active peptides are often, although not always, complementary to their peripheral actions. Atrial natriuretic polypeptide (ANP) is one of these biologically active peptides. Evidence presented here indicates that ANP is involved in the cardiovascular control as a neuropeptide in the central nervous system as well as a circulating hormone in the periphery.

Animals↗
PubMed1986

Leumorphin is a potent inhibitor of vasopressin secretion.

The effects of intracerebroventricular (i.c.v.) injection of leumorphin on the vasopressin secretion induced by angiotensin II or dehydration were studied in conscious unrestrained rats. The vasopressin secretion induced by angiotensin II (100 pmol) was significantly inhibited by the simultaneous injection of leumorphin (6 pmol-600 pmol) in a dose-dependent manner. In 72-hour water-deprived rats, the i.c.v. injection of leumorphin (60 pmol or 600 pmol) significantly suppressed the vasopressin secretion dose-dependently. These results suggest that leumorphin is involved in the regulation of the vasopressin secretion.

Angiotensin II↗
PubMed1986

Centrally administered leumorphin possesses potent depressor activity in conscious rats.

The effect of intracerebroventricular (i.c.v.) administration of leumorphin on basal blood pressure and angiotensin II (AII)-stimulated increase in blood pressure was examined in conscious unrestrained rats. The i.c.v. injection of leumorphin (0.06 and 0.6 nmol) elicited significant depressor effect. The i.c.v. administration of leumorphin with AII (0.1 nmol) significantly attenuated the AII-induced pressor response and, furthermore, lowered blood pressure below the basal level. These results suggest that leumorphin is involved in the central control of blood pressure.

Angiotensin II↗
PubMed1984

Regulatory properties of acetylcholine receptor: evidence for two different inhibitory sites, one for acetylcholine and the other for a noncompetitive inhibitor of receptor function (procaine).

Does the acetylcholine receptor have a specific regulatory (inhibitory) site for the natural receptor ligand acetylcholine? This paper deals with this question. The inhibition of acetylcholine-receptor function by diverse organic cations including local anesthetics such as procaine has been well documented. Evidence indicates that these compounds are noncompetitive inhibitors, enter the open-channel form of the receptor, and block it and that the extent of this blockage depends on the transmembrane voltage of the cell. Recently we reported that in the electroplax of Electrophorus electricus the receptor-controlled transmembrane ion flux is inhibited by acetylcholine in a voltage-dependent, noncompetitive manner. We report here that the Torpedo californica receptor also has an inhibitory site for acetylcholine. The question of whether acetylcholine, which is an organic cation, binds to the same site as other organic cations such as the noncompetitive inhibitor procaine is important and is addressed. The results reported here of chemical kinetic investigations, with receptor-rich E. electricus and T. californica membrane vesicles, indicate that the inhibition of receptor function by acetylcholine and by a local anesthetic, procaine, involves two different receptor sites. The existence of a specific inhibitory site for the natural receptor-ligand acetylcholine suggests that this site can play an important role in the modulation of receptor function and in the regulation of transmission of signals between cells.

Acetylcholine↗