PubMed · 13636765
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M FINKELSTEIN. 1959. Adrenocortical hetero-function.. https://pubmed.ncbi.nlm.nih.gov/13636765/
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gamma-Aminobutyric acid (GABA), a major neurotransmitter in the central nervous system, also acts as a paracrine or autocrine signaling molecule in endocrine tissues such as the pancreatic islets, adenohypophysis, and testis. In the present study, we describe local GABA production and functional GABA(B) receptors in the adrenal cortex, possibly forming an auto- or paracrine GABAergic system. Using immunohistochemistry and RT-PCR, we localized the GABA-synthesizing enzyme glutamate decarboxylase 67 and the vesicular GABA transporter in steroid-producing cells of the human and rat adrenal cortex. Immunocytochemistry, Western blots, and RT-PCR experiments demonstrated the presence of glutamate decarboxylase 67 in the human adrenocortical cell line NCI-H295R. Measurements of glutamate decarboxylase activity confirmed that, in these cells and in rat adrenals, glutamate is decarboxylated to form GABA. In addition, we found expression of the GABA(B(1a)), GABA(B(1e)), and GABA(B(2)) subunits of the heterodimeric GABA(B) receptor in NCI-H295R cells as shown by RT-PCR. GABA(B(1a)) and its truncated splice variant GABA(B(1e)) were also found in human and rat adrenal glands. Immunostaining for the GABA(B(2)) subunit revealed its presence in the human and rat adrenal cortex and in NCI-H295R cells. The GABA(B) receptors we identified were functional because the GABA(B) agonist baclofen inhibited T-type Ca(2+) currents in whole-cell patch clamp experiments on NCI-H295R cells. This effect was blocked by pertussis toxin. Furthermore, the alpha(2)-, alpha(3)-, beta(2)-, beta(3)- gamma(2)-, and epsilon-subunits of the GABA(A) receptor were detected in this cell line by RT-PCR. Hence, we conclude that GABA is synthesized and stored by steroid-producing cells of the adrenal cortex and may influence these cells in a paracrine or autocrine manner.
The adrenal gland is highly vascularized with tightly regulated blood flow that is closely correlated with steroidogenesis. Mechanisms involved in the regulation of adrenal blood flow and vascular tone are largely unknown. The present study characterizes the contractile responses of isolated small cortical arteries from bovine adrenal glands. In endothelium-intact arteries, K(+), the thromboxane mimetic U46619, 5-hydroxytryptamine (5-HT), and endothelin-1 (ET-1) induced concentration-dependent contractions, whereas phenylephrine, norepinephrine, and ACTH were without effect. The EC(50)s for K(+), U46619, 5-HT, and ET-1 were 45 +/- 3 mm, 150 +/- 24 nm, 370 +/- 38 nm, and 2.8 +/- 0.8 nm, respectively. Contractions induced by U46619, 5-HT, and ET-1 were blocked by the thromboxane receptor antagonist SQ 29,548, the 5-HT(2A) receptor antagonist ketanserin, and the ET(A) receptor antagonist BQ 123, respectively. Removal of the endothelium caused a marked leftward shift of concentration responses to high K(+), U46619, 5-HT, and ET-1, and revealed contractile responses to phenylephrine and norepinephrine. In U46619-preconstricted arteries, BQ 123 converted ET-1-induced contractions to relaxations (maximal relaxation of 57 +/- 8%), which were subsequently blocked by the ET(B) receptor antagonist BQ 788. The ET(B)-mediated relaxations were endothelium dependent and inhibited by the nitric oxide synthase inhibitor N-nitro-l-arginine, the cytochrome P450 inhibitor SKF 525A, and high extracellular K(+), but not by the cyclooxygenase inhibitor indomethacin. These results demonstrate that small adrenal cortical arteries are highly responsive to various vasoconstrictor agents. The forceful contractile responses of these arterioles are consistent with their potential role in the regulation of adrenal blood flow.
The existence of paracrine control of steroidogenic activity by adrenochromaffin cells in Triturus carnifex was investigated by in vivo noradrenaline (NA) administration. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the serum levels of aldosterone, NA, and adrenaline (A). In March and July, NA administration increased aldosterone release (from 187.23 +/- 2.93 pg/ml to 878.31 +/- 6.13 pg/ml in March; from 314.60 +/- 1.34 pg/ml to 622.51 +/- 2.65 pg/ml in July) from steroidogenic cells. The cells showed clear signs of stimulation, as evidenced by a strong reduction of lipid content. Moreover, NA administration decreased the mean total number of secretory vesicles in the chromaffin cells in March (from 7.24 +/- 0.18 granules/micro2 to 5.57 +/- 1.88 granules/micro2) and July (from 7.74 +/- 0.74 granules/micro2 to 6.04 +/- 1.13 granules/micro2). In March, however, when T. carnifex chromaffin cells contain both catecholamines, NA (3.88 +/- 0.13 granules/micro2) and A (3.36 +/- 0.05 granules/micro2) in almost equal quantities, NA administration reduced A content (1.29 +/- 1.04 granules/micro2) in the chromaffin cells, enhancing adrenaline secretion (from 681.27 +/- 1.83 pg/ml to 1527.02 +/- 2.11 pg/ml). In July, when the chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/micro2; A: 0.32 +/- 0.13 granules/micro2), NA administration reduced the number of NA granules (5.45 +/- 1.10 granules/micro2), thereby increasing noradrenaline release from the chromaffin cells (from 640.19 +/- 1.65 pg/ml to 1217.0 +/- 1.14 pg/ml). The results of this study indicate that NA influences the steroidogenic cells, eliciting aldosterone release. Noradrenalin effects on the chromaffin cells, increase of NA or A secretion, according to the period of chromaffin cell functional cycle, may be direct and/or mediated through the steroidogenic cells. The existence of intra-adrenal paracrine interactions in T. carnifex is discussed.