Pharmacological modulation of adrenal medullary GABA<sub>A</sub> receptor: consistent with its subunit composition

Parramón, M.; González, M.P.

doi:10.1111/j.1476-5381.1995.tb16676.x

Cited by 9 publications

(6 citation statements)

References 35 publications

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“…It is possible that these studies identified GABA receptor subunits expressed in peripheral nerves contained within these organs. More specific expression of GABA receptor subunits were identified in neuroendocrine cells including pancreatic ␤ (54, 59), pituitary (48), and adrenal cells (44). Indirect pharmacological evidence suggested GABA receptor expression in vascular (22), bladder (19), uterine (2,17,21), and gut (47) smooth muscle in addition to the identification of GABA receptors in the peripheral nerves that innervate these tissues (5,15,46,50).…”

Section: Discussionmentioning

confidence: 97%

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

Mizuta¹,

Xu²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABA(A)) channels and metabotropic (GABA(B)) receptors. GABA(A) channels are ubiquitously expressed in neuronal tissues, and in mature neurons modulate an inward chloride current resulting in neuronal inhibition due to membrane hyperpolarization. In airway smooth muscle (ASM) cells, membrane hyperpolarization favors smooth muscle relaxation. Although GABA(A) channels and GABA(B) receptors have been functionally identified on peripheral nerves in the lung, GABA(A) channels have never been identified on ASM itself. We detected the mRNA encoding of the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, delta-, gamma(1-3)-, pi-, and theta-subunits in total RNA isolated from native human and guinea pig ASM and from cultured human ASM cells. Selected immunoblots identified the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, and gamma(2)-subunit proteins in native human and guinea pig ASM and cultured human ASM cells. The GABA(A) beta(3)-subunit protein was immunohistochemically localized to ASM in guinea pig tracheal rings. While muscimol, a specific GABA(A) channel agonist, did not affect the magnitude or the time to peak contractile effect of substance P, it directly concentration dependently relaxed a tachykinin-induced contraction in guinea pig tracheal rings, which was inhibited by the GABA(A)-selective antagonist gabazine. Muscimol also relaxed a contraction induced by an alternative contractile agonist histamine. These results demonstrate that functional GABA(A) channels are expressed on ASM and suggest a novel therapeutic target for the relaxation of ASM in diseases such as asthma and chronic obstructive lung disease.

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Section: Discussionmentioning

confidence: 97%

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

Mizuta¹,

Xu²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…γ‐Aminobutyric acid (GABA), the main inhibitory neurotransmitter in the CNS, has been shown to be involved in the regulation of catecholamine (CA) secretion from bovine adrenomedullary chromaffin cells (for review see Parramón et al, 1995a) in a neuromodulatory way. GABA is a compound endogenous to the adrenal medulla.…”

mentioning

confidence: 99%

Distribution of γ‐aminobutyric acid receptors in cultured adrenergic and noradrenergic bovine chromaffin cells

Castro

González

Oset-Gasque

2002

J of Neuroscience Research

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Fluorescence imaging techniques for recording cytosolic [Ca(2+)](i) from single chromaffin cells were used to characterize and discriminate between cell subpopulations containing gamma-aminobutyric acid (GABA)(A) and GABA(B) receptor subtypes. By combining this methodology with the immunoidentification of individual chromaffin cells using specific antibodies against tyrosine hydroxylase (TH), phenyl-etanolamine-N-methyl transferase (PNMT), and glutamic acid decarboxylase (GAD) linked to different fluorescent probes, we have been able to ascribe single-cell calcium responses to identified adrenergic and noradrenergic chromaffin cells. GAD enzyme is present in 30% of the chromaffin cell population, located primarily in adrenergic cells; 86% of GAD(+) cells were also PNMT(+). GAD expression was not correlated with the presence of GABA receptors. GABA-responsive cells were found with equal frequency in the GAD(+) and GAD(-) groups. However, the expression of GABA receptors was correlated with the adrenergic phenotype. [Ca(2+)](i) responses to GABA were found more frequently in adrenergic than in noradrenergic cells. GABA(A) receptors are more evenly distributed; about 90% of GABA-responsive cells have them. GABA(B) receptors have a more restricted distribution (present in 45% of responding cells). The coexpression of both GABA(A) and GABA(B) subtypes is the rule; only a minor subpopulation (about 12%) displays exclusively GABA(B) receptors. GABA receptor subtypes are distributed in a similar way when chromaffin cells are separated according to GAD(+)/GAD(-) or PNMT(+)/PNMT(-) classifications, with only minor differences. These data indicate that the intrinsic GABAergic system in the adrenal medulla is not designed as a paracrine model in which a group of cells specializes in transmitter synthesis and a different group serves as a specific target.

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“…The adrenal medulla contains GABA A receptor ·1 and ß1-3 subunits, but not ·2 or ·3 subunits, as determined from cDNA library screening and Northern blots [43]. More recent results suggest the presence of ·4 and Á2 as well [44].…”

Section: Discussionmentioning

confidence: 93%

GABA<sub>A</sub> Receptor Subunit mRNAs in Rat Superior Cervical Ganglia

Liu

Burt²

1998

Pharmacology

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γ-Aminobutyric acid (GABA), one of the most important neurotransmitters in the brain, is also found in the periphery. GABA_A receptors are chloride channels opened by GABA whose presence in the rat superior cervical ganglion has been indicated by functional and binding measurements. We describe the first molecular data on the possible subunit composition of these receptors, detecting mRNAs for 12 subunits (α1–5, β1–3, γ1–3, δ) by reverse-transcriptase polymerase chain reaction. Preliminary quantitation gave highest levels (in descending order) for the γ2 (both short and long forms), β3, γ3, and α1 subunits.

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Pharmacological modulation of adrenal medullary GABA_A receptor: consistent with its subunit composition

Cited by 9 publications

References 35 publications

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

Distribution of γ‐aminobutyric acid receptors in cultured adrenergic and noradrenergic bovine chromaffin cells

GABA<sub>A</sub> Receptor Subunit mRNAs in Rat Superior Cervical Ganglia

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Pharmacological modulation of adrenal medullary GABAA receptor: consistent with its subunit composition

Cited by 9 publications

References 35 publications

GABAAreceptors are expressed and facilitate relaxation in airway smooth muscle

GABAAreceptors are expressed and facilitate relaxation in airway smooth muscle

Distribution of γ‐aminobutyric acid receptors in cultured adrenergic and noradrenergic bovine chromaffin cells

GABA<sub>A</sub> Receptor Subunit mRNAs in Rat Superior Cervical Ganglia

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Pharmacological modulation of adrenal medullary GABA_A receptor: consistent with its subunit composition

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle