Glucocorticoids inhibit acetylcholine-induced current in chromaffin cells

Inoue, Masanobu; Kuriyama, Hirosi

doi:10.1152/ajpcell.1989.257.5.c906

Cited by 39 publications

(18 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pharmacological features of the muscarinic current At a membrane potential of -70 mV, bath application of nicotine, but not of muscarine, produced an inward current, but when the membrane potential was held at -40 mV, both agents evoked an inward current with an associated increase in current noise (Inoue & Kuriyama, 1989). As shown in Fig.…”

Section: Resultsmentioning

confidence: 79%

Muscarinic receptor is coupled with a cation channel through a GTP‐binding protein in guinea‐pig chromaffin cells.

Inoue

Kuriyama

1991

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. The ionic current evoked by muscarinic receptor agonists was investigated in dispersed chromaffin cells of the guinea-pig adrenal medulla using the whole-cell version of the patch-clamp procedure.2. Muscarine or oxotremorine (0-03-10 #M) produced an inward current associated with an increase in current noise at a holding potential of -40 mV. The relationship between current and oxotremorine concentration fitted well to a rectangular hyperbole with an apparent dissociation constant (KA) of 0-23 JiM.3. The muscarinic antagonists pirenzepine (0-1 ftM) and AF-DX 116 (0 3 /LM) shifted the dose-response curve to the right in a parallel manner. Dissociation constants (KB) for pirenzepine and AF-DX 116 were estimated to be 50 and 70 nm, respectively.4. The current-voltage relation for the current induced by muscarine had a negative slope below -30 or -20 mV, and the current reversed its polarity at 0-4 + 0-8 mV (n = 4) in standard salt solution. Removal of Mg2+ or Ca2+ from the perfusate did not modify the muscarinic current-voltage relationship.5. When Na+ in the bath solution was replaced with Tris, the muscarinic current-voltage relationship shifted to the left (the hyperpolarizing direction); the current reversed its polarity at -18-7 + 1-2 mV in a solution containing 72 mM-Na+ (three cells) and at -57-5 + 2-7 mV in nominally Na+-free solution (three cells). When Ca21 was replaced by Mg2+, in Na+-free solution, an inward current was not evoked by muscarinic stimulation.6. Tetraethylammonium (TEA; 0-03-3 mM) reduced the muscarinic current at -40 mV, and the KD value was 0-34 mm with a Hill coefficient of 1. Barium (4 mM) reduced the current to 0-69 + 0-06 of control (n = 3).7. When the recording electrodes contained guanosine-5'-O-(3-thiophosphate) (GTPyS, 100 UM), an inward current developed at -55 mV during the first few minutes after breaking into the cell interior. This inward current was associated with

show abstract

Section: Resultsmentioning

confidence: 79%

Muscarinic receptor is coupled with a cation channel through a GTP‐binding protein in guinea‐pig chromaffin cells.

Inoue

Kuriyama

1991

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Na + (53,98), often in combination with other ions such as K + (97), H + (54,(99)(100)(101), or Cl − (92,(102)(103)(104), has also been reported to be affected. These ion fluxes sometimes result in cellular pH changes (53,89), or the raising or lowering of membrane potentials sufficient to trigger, inhibit, or change the firing rate of action potentials in permissive tissues (31-34, 68,70). Practically the same spectrum of hormones and tissues is involved in these further examples.…”

Section: Cellular Mechanisms Associated With Membrane-initiated Steromentioning

confidence: 99%

Membrane-Initiated Steroid Actions and the Proteins that Mediate Them

Watson

Gametchu

1999

Experimental Biology and Medicine

123

View full text Add to dashboard Cite

Membrane-initiated or nongenomic activities of steroids contribute to the effects of steroids on a wide variety of target organs, including those with low receptor numbers, recently discovered due to the increased sensitivity of new measurement techniques. Membrane-initiated responses are the cell's rapid and first response to steroids. The responses that emanate from the membrane can have direct functional consequences, such as secretion of other peptide hormones or rapid behavioral changes. Other rapid responses are prerequisites for subsequent genomic responses. The wide variety of signal transduction schemes employed by various tissues and hormones are summarized and discussed in terms of the identity of proteins that mediate these responses. Probable mixed binding systems for steroids in plasma membranes are compared to similar multiple hormone-binding protein systems in extracellular fluids and inside cells. These issues are related to steroid-dependent tumor growth, developmental and therapeutic apoptosis, and the actions of endocrine disrupters. The integration of membrane-initiated effects with genomic mechanisms results in the complete cellular response to steroids.

show abstract

“…In addition, progesterone attenuates cation fluxes evoked by excitatory amino acids in cerebellar Purkinje cells (7) and current induced by acetylcholine (AcCho) in chromaffin cells (8) and in reconstituted brain nicotinic AcCho receptor (nAcChoR) (9). In contrast, pregnenolone inhibits GABAA receptors in rat cortex neurons (10) and a progesteroneinduced reduction of glycine-evoked current has been reported for spinal cord neurons (11).…”

mentioning

confidence: 99%

Progesterone modulates a neuronal nicotinic acetylcholine receptor.

Valera¹,

Ballivet²,

Bertrand³

1992

Proc. Natl. Acad. Sci. U.S.A.

243

108

View full text Add to dashboard Cite

The major brain nicotinic acetylcholine receptor is assembled from two subunits termed a4 and nal. When expressed in Xenopus oocytes, these subunits reconstitute a functional acetylcholine receptor that is inhibited by progesterone levels similar to those found in serum. In this report, we show that the steroid interacts with a site located on the extracellular part of the protein, thus confirming that inhibition by progesterone is not due to a nonspecific perturbation of the membrane bilayer or to the activation of second messengers. Because inhibition by progesterone does not require the presence of agonist, is voltage-independent, and does not alter receptor desensitization, we conclude that the steroidis not an open channel blocker. In addition, we show that progesterone is not a competitive inhibitor but may interact with the acetylcholine binding site and that its effect is independent of the ionic permeability of the receptor.Steroid hormones are synthesized from cholesterol in the adrenal gland (the gluco-and mineralocorticoids) and in the gonads and placenta (androgens and estrogens). Their lipophilicity explains their passage of the blood-brain barrier. Steroids have also been demonstrated to reduce brain activity and alphaxalone is used clinically. The potency of anesthetics has been correlated with their liposolubility (2, 3), yet the molecular basis of these effects remains obscure.Some steroids, including 5a-pregnan-3a-hydroxy-20-one, enhance chloride fluxes at the y-aminobutyric acid (GABA) synapses of the type A GABA (GABAA) receptors (4, 5) and in transfected cells expressing GABAA receptors (6). In addition, progesterone attenuates cation fluxes evoked by excitatory amino acids in cerebellar Purkinje cells (7) and current induced by acetylcholine (AcCho) in chromaffin cells (8) and in reconstituted brain nicotinic AcCho receptor (nAcChoR) (9). In contrast, pregnenolone inhibits GABAA receptors in rat cortex neurons (10) and a progesteroneinduced reduction of glycine-evoked current has been reported for spinal cord neurons (11).The aim of this work is to investigate the mode of action of progesterone on the major brain neuronal nAcChoR a4/nal reconstituted in Xenopus oocytes. MATERIALS AND METHODSOocyte preparation and recording procedures were as described (12). Data acquisition, storage, and analysis were done on an IBM-PC/AT using the software DATAC (13).Inhibition curves were fitted to the empirical Hill equation. Inhibition by progesterone as a function of the AcCho concentration was fitted by using a Michaelis equation in the form:where y is the normalized current, a is a constant, x is the AcCho concentration, and IC50 is apparent inhibition constant. All steroids were purchased from Sigma. Stock solutions of steroids and progesterone-3-(O-carboxymethyl)oxime (P-3; Sigma P-3277) were at 0.01 M, in ethanol. Stock solutions were kept at -20TC and diluted in OR-2 (12) just before use. P-3-conjugated bovine serum albumin (P-3-BSA; Sigma P-4778, progesterone/BSA ratio = 38:1) and Hahyd...

show abstract

Glucocorticoids inhibit acetylcholine-induced current in chromaffin cells

Cited by 39 publications

References 24 publications

Muscarinic receptor is coupled with a cation channel through a GTP‐binding protein in guinea‐pig chromaffin cells.

Muscarinic receptor is coupled with a cation channel through a GTP‐binding protein in guinea‐pig chromaffin cells.

Membrane-Initiated Steroid Actions and the Proteins that Mediate Them

Progesterone modulates a neuronal nicotinic acetylcholine receptor.

Contact Info

Product

Resources

About