GABA of CNS origin in the rat anterior pituitary inhibits prolactin secretion

Racagni, Giorgio; Apud, José; Locatelli, Vittorio; Cocchi, Daniela; Nisticò, G; Giorgio, Rosa María Di; Müller, Eugenio E.

doi:10.1038/281575a0

Cited by 94 publications

(45 citation statements)

References 28 publications

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“…GABA is synthesized by the hypophysis in vitro (12,13). Furthermore, glutamic acid decarboxylase (GluDCase, the GABA biosynthetic enzyme) activity has been found in the neurointermediate lobe (14) but not in the anterior lobe (5). GABA receptors appear to be present in the anterior lobe (15) and on axons of hypothalamicneurohypophysial neurons (16).…”

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“…Measurable amounts of endogenous GABA have been reported in the anterior pituitary lobe, but much higher amounts are present in the posterior lobe (5,11). GABA is synthesized by the hypophysis in vitro (12,13).…”

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confidence: 99%

“…These data provide biochemical and morphological evidence for a central GABAergic innervation of neural and intermediate lobes of the hypophysis. y-Aminobutyric acid (GABA) has been implicated in modulating secretion of pituitary hormones (1)(2)(3)(4)(5) and hypothalamichypophysial hormones (6,7). GABAergic neuroendocrine modulation may occur in the hypothalamus, for example, in the median eminence, where GABAergic terminals are present (8), or directly at the pituitary level (5,9,10).…”

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Central GABAergic innervation of neurointermediate pituitary lobe: biochemical and immunocytochemical study in the rat.

Oertel¹,

Mugnaini²,

Tappaz³

et al. 1982

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

128

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Activity of glutamic acid decarboxylase GluDCase, the biosynthetic enzyme of y-aminobutyric acid (GABA), was y-Aminobutyric acid (GABA) has been implicated in modulating secretion of pituitary hormones (1-5) and hypothalamichypophysial hormones (6, 7). GABAergic neuroendocrine modulation may occur in the hypothalamus, for example, in the median eminence, where GABAergic terminals are present (8), or directly at the pituitary level (5, 9, 10).Measurable amounts of endogenous GABA have been reported in the anterior pituitary lobe, but much higher amounts are present in the posterior lobe (5, 11). GABA is synthesized by the hypophysis in vitro (12, 13). Furthermore, glutamic acid decarboxylase (GluDCase, the GABA biosynthetic enzyme) activity has been found in the neurointermediate lobe (14) but not in the anterior lobe (5). GABA receptors appear to be present in the anterior lobe (15) and on axons of hypothalamicneurohypophysial neurons (16). However, the organization of GABAergic structures in the hypophysis has not been examined.In the present study, we have measured GluDCase activity in the anterior and neurointermediate pituitary lobes, with and without stalk transection, and used a specific antiserum to rat brain GluDCase (17) to localize GluDCase in the hypophysis. MATERIALS AND METHODSSprague-Dawley male rats (body weight 150-200 g) were purchased from Zivic Miller (Allison Park, PA). The rats were subdivided into three groups: unoperated, pituitary-stalk transected, and sham operated. Six days after surgery, rats from the three groups (see Table 1) were decapitated, the brains were removed, and the pituitary glands were dissected out. The neurointermediate lobe was separated from the anterior lobe. The tissues were homogenized with a glass/glass homogenizer on ice, in 150 ,ul of a buffer solution containing 20 mM potassium phosphate buffer (pH 7.2), 1 mM 2-aminoethylisothiouronium bromide hydrobromide, 0.2 mM. pyridoxal phosphate, 0.1 mM EDTA, and 0.25% Triton X-100. Aliquots (30-40 p1) of the whole homogenate or the supernatant fluid, obtained after centrifugation for 30 min at 25,000 X g at 4°C, were assayed for GluDCase (18) and protein (19).Four unoperated, two sham-operated, and four stalk-transected rats were used for light microscopy, and four unoperated rats were used for electron microscopy. The animals were fixed by perfusion through the ascending aorta with 200 ml of a solution containing 1% formaldehyde and 0.5% glutaraldehyde in 0.065 M sodium phosphate buffer (pH 7.3 at 37°C, delivered at a pressure of 80 cm ofwater) followed by 300 ml of 4% formaldehyde in the same buffer at 20°C. The dissected pituitary glands were sectioned on a Vibratome, and the sections, after treatment with 3% H202 in 10% methanol to eliminate endogenous peroxidase-like activity, were processed with the unlabeled antibody-enzyme method of Sternberger (20) for light and electron microscopy. This procedure, described in detail elsewhere (21), uses our GluDCase antiserum S3 (second bleed) (17) at dilutions of 1...

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Central GABAergic innervation of neurointermediate pituitary lobe: biochemical and immunocytochemical study in the rat.

Oertel¹,

Mugnaini²,

Tappaz³

et al. 1982

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

128

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“…GABA, like DA, was found to inhibit prolactin secretion at the adenohypophysial level [15,28,37,41]. This effect is probably mediated by high affinity receptors [14] which seem to act independently from DA receptors [11].…”

Section: Discussionmentioning

confidence: 99%

“…This effect is probably mediated by high affinity receptors [14] which seem to act independently from DA receptors [11]. Benzodi azepines might enhance the inhibitory effect of GABA on prolactin-secreting pituitary cells; GABAergic neurones are present in the hypothalamus [45,46] and there is evidence that adenohypophysial GABA originates from the CNS [37]. Whether benzodiazepines affect prolactin secretion through DA or GABA or both remains open.…”

Section: Discussionmentioning

confidence: 99%

Benzodiazepine Antagonist Ro 15-1788 Counteracts the Prolactin-Lowering Effects of Other Benzodiazepines in Rats

Lotz¹

1982

Neuroendocrinology

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A number of centrally active benzodiazepines lowered baseline serum prolactin concentrations after oral administration to male rats. The increase of circulating prolactin levels elicited by oral administration of various neuroleptic agents was also reduced by prior or simultaneous oral administration of several benzodiazepines in a dose-dependent manner. Since both effects were prevented by simultaneous administration of the benzodiazepine antagonist Ro 15-1788 they are probably mediated by central benzodiazepine receptors which interfere with aminergic mechanisms governing serum prolactin.

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GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs.

et al. 1989

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Cloned cDNAs encoding two new beta subunits of the rat and bovine GABAA receptor have been isolated using a degenerate oligonucleotide probe based on a highly conserved peptide sequence in the second transmembrane domain of GABAA receptor subunits. The beta 2 and beta 3 subunits share approximately 72% sequence identity with the previously characterized beta 1 polypeptide. Northern analysis showed that both beta 2 and beta 3 mRNAs are more abundant in the brain than beta 1 mRNA. All three beta subunit encoding cDNAs were also identified in a library constructed from adrenal medulla RNA. Each beta subunit, when co‐expressed in Xenopus oocytes with an alpha subunit, forms functional GABAA receptors. These results, together with the known alpha subunit heterogeneity, suggest that a variety of related but functionally distinct GABAA receptor subtypes are generated by different subunit combinations.

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GABA of CNS origin in the rat anterior pituitary inhibits prolactin secretion

Cited by 94 publications

References 28 publications

Central GABAergic innervation of neurointermediate pituitary lobe: biochemical and immunocytochemical study in the rat.

Central GABAergic innervation of neurointermediate pituitary lobe: biochemical and immunocytochemical study in the rat.

Benzodiazepine Antagonist Ro 15-1788 Counteracts the Prolactin-Lowering Effects of Other Benzodiazepines in Rats

GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs.

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