scholarly journals Regulation of the cerebellar inositol 1,4,5-trisphosphate receptor by univalent cations

2004 ◽  
Vol 381 (2) ◽  
pp. 423-428
Author(s):  
Jean-François COQUIL ◽  
Samantha BLAZQUEZ ◽  
Sabrina SOAVE ◽  
Jean-Pierre MAUGER
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Specific Binding ◽  
Dose Response Curve ◽  
Dependent Manner ◽  
Univalent Cations ◽  
Physiological Concentration ◽  
Number Of Binding Sites ◽  
Trisphosphate Receptor ◽  
Dose Dependent

In the present study we investigated the effects of K+ and other univalent cations on [3H]InsP3 {[3H]Ins(1,4,5)P3} binding to sheep cerebellar microsomes. In equilibrium binding experiments performed over 4 s at pH 7.1 and 20 °C, the addition of K+ to the binding medium decreased the affinity and increased the total number of binding sites for InsP3 in a dose-dependent manner. At low InsP3 concentration (0.5 nM) these effects resulted in a biphasic dose–response curve, with maximal binding at about 75 mM K+. In contrast, the dose–response curve calculated for InsP3 at the physiological concentration of 5 μM, was linear up to 200 mM K+. Univalent inorganic cations stimulated [3H]InsP3 binding to various extents, with the following descending order of efficiency at 75 mM: Cs+≈Rb+≈K+>Na+>Li+. The effect of K+ on InsP3R affinity was rapidly reversed upon cation removal. We were therefore also able to demonstrate that K+ increased Bmax (maximal specific binding) by pre-treating microsomes with K+ before measuring [3H]InsP3 binding in the absence of that cation. The increase in Bmax was reversible, but this reversal occurred less rapidly than the change in affinity. These results are consistent with a process by which K+ reversibly converted very low-affinity sites into sites with higher affinity, making them detectable in competitive binding experiments. They suggest that interconversion between these two affinity states constitutes the basis of a K+-controlled regulatory mechanism for cerebellar InsP3R.

scholarly journals Inhibition by somatostatin of amylase secretion induced by calcium and cyclic AMP in rat pancreatic acini

1994 ◽  
Vol 304 (2) ◽  
pp. 531-536 ◽  
Author(s):  
H Ohnishi ◽  
T Mine ◽  
I Kojima
Keyword(s):  
Cyclic Amp ◽  
G Protein ◽  
Pertussis Toxin ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Amylase Secretion ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Pancreatic Acini

It has recently been shown that somatostatin inhibits amylase secretion from isolated pancreatic acini by reducing cyclic AMP (cAMP) production [Matsushita, Okabayashi, Hasegawa, Koide, Kido, Okutani, Sugimoto and Kasuga (1993) Gastroenterology 104, 1146-1152]. To date, however, little is known as to the other mechanism(s) by which somatostatin inhibits amylase secretion in exocrine pancreas. To investigate the action of somatostatin independent of cAMP generation, we examined the effect of somatostatin in isolated rat pancreatic acini stimulated by 1 microM calcium ionophore A23187 and 1 mM 8-bromo-cyclic AMP (8Br-cAMP). Somatostatin inhibited amylase secretion evoked by a combination of A23187 and 8Br-cAMP in a dose-dependent manner. The maximum inhibition was obtained by 10(-7) M somatostatin, and at this concentration somatostatin inhibited the effect of A23187 and 8Br-cAMP by approximately 30%. In electrically permeabilized acini, an elevation of free calcium concentration resulted in an increase in amylase secretion and cAMP enhanced the secretion evoked by calcium. cAMP shifted the dose-response curve for calcium-induced secretion leftwards and elevated the peak value of secretion. Somatostatin inhibited the effect of cAMP on calcium-induced amylase secretion by shifting the dose-response curve to the right. To determine the involvement of a G-protein(s), we examined the effect of somatostatin in acini pretreated with pertussis toxin. Pretreatment of acini with pertussis toxin completely blocked somatostatin-inhibition of amylase-secretion evoked by A23187 and 8Br-cAMP. These results indicate that somatostatin decreases amylase secretion induced by cAMP and calcium by reducing the calcium sensitivity of exocytosis. A pertussis toxin-sensitive G-protein is also involved in this step.

scholarly journals Stimulation of hepatic lipogenesis and acetyl-coenzyme A carboxylase by vasopressin

1981 ◽  
Vol 198 (3) ◽  
pp. 485-490 ◽  
Author(s):  
F Assimacopoulos-Jeannet ◽  
R M Denton ◽  
B Jeanrenaud
Keyword(s):  
Fatty Acid ◽  
Dose Response ◽  
Fatty Acid Synthesis ◽  
Response Curve ◽  
Acid Synthesis ◽  
Dose Response Curve ◽  
Dependent Manner ◽  
Hepatic Lipogenesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa

The effect of vasopressin on the short-term regulation of fatty acid synthesis was studied in isolated hepatocytes from rats fed ad libitum. Vasopressin stimulates fatty acid synthesis by 30-110%. This increase is comparable with that obtained with insulin. Angiotensin also stimulates fatty acid synthesis, whereas phenylephrine does not. The dose-response curve for vasopressin-stimulated lipogenesis is similar to the dose-response curve for glycogenolysis and release of lactate plus pyruvate. Vasopression also stimulates acetyl-CoA carboxylase activity in a dose-dependent manner. Vasopressin does not relieve glucagon-inhibited lipogenesis, whereas insulin does. The action of vasopressin on hepatic lipogenesis is decreased, but not suppressed, in Ca2+-depleted hepatocytes. The results suggest that vasopressin acts on lipogenesis by increasing availability of lipogenic substrate (lactate + pyruvate) and by activating acetyl-CoA carboxylase.

Substance P potentiates calcium channel modulation by somatostatin in chick sympathetic ganglia

1994 ◽  
Vol 72 (6) ◽  
pp. 2683-2690 ◽  
Author(s):  
A. Golard ◽  
L. Role ◽  
S. A. Siegelbaum
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Substance P ◽  
Dose Response ◽  
Calcium Current ◽  
Response Curve ◽  
Dose Response Curve ◽  
Dependent Manner ◽  
Kinase C ◽  
Voltage Dependent

1. The whole cell patch clamp was used to measure calcium current in isolated chick sympathetic ganglion neurons. Previous results showed that somatostatin inhibits calcium currents (ICa) in a voltage-dependent manner. The effect of somatostatin rapidly desensitizes. In addition, the action of somatostatin on the calcium current is inhibited by activation of protein kinase C (PKC). Because substance P (SP) has been shown to activate PKC in the chick sympathetic neurons, we here test the effects of SP on the calcium current and on the modulatory action of somatostatin. 2. At a concentration of 1 microM, SP had small, variable effects on ICa. 3. SP in the presence of guanosine 5'-triphosphate-gamma-S, or at higher concentrations (10 microM), inhibited ICa in a voltage-dependent manner, similar to the action of somatostatin. 4. Rather than inhibiting the action of somatostatin, SP (1 microM) potentiated the response to somatostatin. This effect of SP was only observed after the response to somatostatin had partially desensitized. SP had no effect on nondesensitized responses to somatostatin. 5. Desensitization of the somatostatin response involved a shift in its dose-response curve toward higher somatostatin concentrations as well as a decrease in the maximal response. SP appears to counteract the shift of the dose-response curve selectively. 6. The potentiation of the somatostatin response by SP is blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), but not by Calphostin C, Compound 5, k252a, protein kinase C (PKC)19-36, or adenylyl-imidodiphosphate (AMP-PNP), suggesting that phosphorylation is not involved and that the H-7 action does not depend on kinase inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Differential proliferative responses of cultured Schwann cells to axolemma- and myelin-enriched fractions. I. Biochemical studies.

1984 ◽  
Vol 99 (6) ◽  
pp. 2309-2313 ◽  
Author(s):  
J E Yoshino ◽  
M P Dinneen ◽  
B L Lewis ◽  
J H Meador-Woodruff ◽  
G H Devries
Keyword(s):  
Schwann Cells ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Hill Coefficient ◽  
Maximal Response ◽  
Response Curves ◽  
Cultured Schwann Cells ◽  
Rat Brainstem ◽  
Dose Dependent

Cultured rat Schwann cells were treated for 72 h with axolemma- and myelin-enriched fractions prepared from rat brainstem. [3H]Thymidine was added to the cultures 48 h before the termination of the experiment. Although, both fractions produced a dose-dependent uptake of label into Schwann cells, the shape of the dose response curves and rates at which [3H]thymidine was incorporated were different. The axolemma-enriched fraction produced a sigmoid dose response curve with a Hill coefficient of 2.05. The dose response curve for myelin rose sharply and saturated at a level that was approximately 50% of the maximal response observed with axolemma. Schwann cells that had been treated with axolemma exhibited little change in the rate of [3H]thymidine incorporation from 36-72 h after the addition of the membranes. In contrast, Schwann cells accumulated label three times faster during the 48-72-h period following the addition of myelin to the cultures when compared with the rate during the preceding 12-h interval. Furthermore, the mitogenic activity of the myelin-enriched fraction was decreased by the addition of ammonium chloride, a lysosomal inhibitor, whereas the activity of the axolemmal fraction was not impaired.

Beta 2-adrenoceptor-mediated positive dromotropic effects on atrioventricular node of dogs

1992 ◽  
Vol 262 (1) ◽  
pp. H123-H129
Author(s):  
S. Motomura ◽  
K. Hashimoto
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Atrioventricular Node ◽  
Dose Response Curve ◽  
Av Node ◽  
Adrenoceptor Agonist ◽  
Beta 2 ◽  
The Right ◽  
Dose Dependent ◽  
Isoproterenol Hydrochloride

The functional significance of beta 2-adrenoceptors in atrioventricular (AV) nodal conduction was investigated by using canine isolated blood-perfused AV node preparations. Dose-dependent shortening of the atrio-His bundle (A-H) interval by dl-procaterol hydrochloride hemihydrate (0.03-1 nmol) injected intra-arterially into the AV node artery was affected little by an infusion of dl-atenolol (10 nmol/min) into the same artery, whereas the dose-response curve for the positive dromotropic effect of procaterol was shifted markedly to the right by approximately 1.5 and 2.5 log units with ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylamino-bu tan-2-ol]- hydrochloride (1 and 10 nmol/min). The positive dromotropic effect of dl-T-1583 [alpha-(3,4,5-trimethoxyphenethylaminomethyl)-3,4-dihydroxybenzyl- alcohol] hydrochloride (30-300 pmol), a selective beta 1-adrenoceptor agonist, was shifted to the right by approximately 1.2 log units with dl-atenolol (10 nmol/min) but was affected little by ICI 118551 (10 nmol/min). The dose-response curve for l-isoproterenol hydrochloride (3-100 pmol) was shifted to the right by 0.7 log unit with ICI 118551 (10 nmol/min) and by 1.7 log units with atenolol (10 nmol/min). The dose-response curve for dl-norepinephrine (0.03-1 nmol) was shifted to the right by 1.0 log unit with atenolol only, whereas the curve for l-epinephrine (0.03-1 nmol) was shifted by 0.45 log unit with ICI 118551 (10 nmol/min). These results suggest that both beta 1- and beta 2-adrenoceptors, which coexist on the AV node, play a functional role in AV nodal conduction.

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

HYPERTROPHIC ADRENALS AND THEIR RESPONSE TO STRESS AFTER LESIONS IN THE MEDIAN EMINENCE OF TOTALLY HYPOPHYSECTOMIZED PIGEONS

1961 ◽  
Vol 37 (4) ◽  
pp. 565-576 ◽  
Author(s):  
Richard A. Miller
Keyword(s):  
Dose Response ◽  
Median Eminence ◽  
Response Curve ◽  
Liver Parenchyma ◽  
Dose Response Curve ◽  
Pars Distalis ◽  
Adrenal Enlargement ◽  
Response To Stress ◽  
Lethal Doses ◽  
Chromaffin Tissue

ABSTRACT Four per cent formaldehyde, insulin, or epinephrine in oil was injected for 5 days into pigeons subjected to varying degrees of hypophysectomy alone or together with large lesions in the median eminence and hypothalamus. Adrenals atrophied after the removal of the pars distalis alone or together with the neurohypophysis in untreated pigeons but showed markedly hypertrophic interrenal tissue (cortex in mammals) after treatment with formaldehyde or insulin. The slope of the dose-response curve was similar in operated and unoperated pigeons. The accumulation of bile in the liver parenchyma, which may occur after removal of the pars distalis, is an endogenous stress which was associated regularly with adrenal hypertrophy. After very large lesions of the median eminence and ventral hypothalamus in addition to total hypophysectomy, adrenals hypertrophied rather than atrophied, and the response to formaldehyde paralleled that in intact and »hypohysectomized« pigeons. Interrenal tissue was stimulated regularly; chromaffin tissue was partially degranulated, sometimes showed hyperplasia with colchicine, but only occasionally appeared hypertrophied. Epinephrine in nearly lethal doses caused only minimal adrenal enlargement. After adrenal denervation followed by hypophysectomy, the adrenals were still stimulated by formaldehyde. It appears that the interrenal tissue of the pigeon responds to a humoral stimulus not of hypophyseal origin in the absence of the hypophyseal-hypothalamic system.

ANTI-OVULATORY ACTIVITY OF STEROIDS ADMINISTERED BY GAVAGE IN THE ADULT OESTRUS RABBIT

1963 ◽  
Vol 42 (2_Suppl) ◽  
pp. S17-S30
Author(s):  
Fred A. Kind ◽  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Active Compound ◽  
Subcutaneous Injection ◽  
Response Curve ◽  
Parent Compound ◽  
Dose Response Curve ◽  
Relative Potency ◽  
Reference Standard ◽  
Highly Active ◽  
Dose Levels

ABSTRACT Thirty-seven steroids have been studied as orally effective inhibitors of ovulation in the mated oestrus rabbit. Norethisterone served as the reference standard and a dose response curve was established between the 0.31 and 1.25 mg dose levels. Nine highly active anti-ovulatory compounds are described listed in a decreasing order of potency with norethisterone having the arbitrary value of one: 6-chloro-Δ6-dehydro-17α-acetoxyprogesterone (35), 6α-methyl-Δ1-dehydro-17α-acetoxyprogesterone (≥ 10), 6-fluoro-Δ6-dehydro-17α-acetoxyprogesterone(9), 6-methyl-Δ6-dehydro-17α-acetoxyprogesterone (5), Δ6-dehydro-17α-acetoxyprogesterone (≥ 3), 6α-methyl-17α-acetoxyprogesterone (2.6), 6-chloro-Δ1,6-bisdehydro-17α-acetoxyprogesterone (≥ 2), 2-hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one (≥ 2), and 6α-fluoro-16α-methyl-17α-acetoxyprogesterone (≥ 1.25). The anti-ovulatory activity of a compound was not related necessarily to the progestational activity of a compound nor to the anti-gonadotrophic activity as measured in parabiotic rats. 6-Chloro-Δ60dehydro-17-acetoxyprogesterone was as effective by gavage as previously shown by subcutaneous injection. 2-Hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one was at least 2.5 times more active by gavage than by injection. While 17α-acetoxyprogesterone was a very weak anti-ovulatory steroid, modifications of the structure by addition of methyl or halogen at the 6α position with or without unsaturation greatly increased the activity. 6-Chloro-Δ6-dehydro-27α-acetoxyprogesterone was the most active compound in this series showing a relative potency of 3500 times that of the parent compound 17α-acetoxyprogesterone.

Sign in / Sign up

Export Citation Format

Share Document