GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects

The activation of pituitary GABAB receptors by the specific agonist baclofen inhibits pituitary hormone secretion in vitro. Here we studied the mechanism of action of GABAB receptors in rat adenohypophysis. Anterior pituitary cells were obtained by trypsinization and were either plated for hormonal...

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Publicado: 2001
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v73_n5_p334_LuxLantos
http://hdl.handle.net/20.500.12110/paper_00283835_v73_n5_p334_LuxLantos
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spelling paper:paper_00283835_v73_n5_p334_LuxLantos2023-06-08T14:55:04Z GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects Calcium Cyclic AMP G proteins GABAB receptors Gamma-aminobutyric acid Gamma-aminobutyric acid receptors Gonadotropin-releasing hormone Gonadotropins Prolactin Thyrotropin-releasing hormone 2 hydroxysaclofen 4 aminobutyric acid B receptor 4 aminobutyric acid B receptor blocking agent baclofen barium calcium channel calcium ion cyclic AMP dopamine forskolin fura 2 acetoxymethyl ester gonadorelin guanine nucleotide binding protein hypophysis hormone luteinizing hormone nifedipine pertussis toxin potassium channel blocking agent prolactin protirelin tetrylammonium trypsin verapamil adenohypophysis animal cell animal tissue article calcium cell level controlled study female hypophysis cell luteinizing hormone release nonhuman presynaptic nerve priority journal proestrus prolactin release rat receptor binding Animals Baclofen Barium Compounds Calcium Calcium Channel Blockers Cells, Cultured Chlorides Cyclic AMP Dopamine Female Forskolin Luteinizing Hormone Pertussis Toxin Pituitary Gland, Anterior Potassium Channel Blockers Potassium Chloride Proestrus Prolactin Rats Receptors, GABA-B Tetraethylammonium Thyrotropin-Releasing Hormone Virulence Factors, Bordetella The activation of pituitary GABAB receptors by the specific agonist baclofen inhibits pituitary hormone secretion in vitro. Here we studied the mechanism of action of GABAB receptors in rat adenohypophysis. Anterior pituitary cells were obtained by trypsinization and were either plated for hormonal studies and cAMP determination or incubated in FURA 2AM for calcium measurements. Baclofen (BACL: 1·10-5 M) significantly inhibited basal and thyrotropic releasing hormone (TRH)-stimulated (1·10-7 M) PRL secretion in anterior pituitary cells from proestrous rats. In the presence of pertussis toxin (PTX: 150 ng/ml, 20 h), which leads to the uncoupling of the Gi/o-protein from the receptor, both effects of BACL were abolished while the effect of dopamine (DA: 1·10-8 M), used as an inhibitory control, was reduced from 70 to 25%. PTX also reversed BACL-induced inhibition of gonadotropin-releasing hormone (GnRH)-elicited luteinizing hormone (LH) secretion in anterior pituitary cells from 15-day-old female rats. In addition, though working in a pituitary mixed cell population, in which only some cell types possess GABAB receptors, BACL (1·10-5 M) attenuated the forskolin-induced (0.5 μM) increase in cAMP. This effect was prevented by co-incubation with the antagonist 2 hydroxysaclofen and by preincubation with PTX. BACL (5·10-5 M) and DA (5·10-7 M) inhibited basal intracellular calcium concentrations ([Ca2+]i) in pituitary cells and the effect of the latter was significantly stronger. The effect of BACL on [Ca2+]i was abolished after preincubation with PTX. In the presence of the potassium channel blocking agents barium (200 μM and 1 mM) and tetraethylammonium (10 mM), BACL was still able to inhibit [Ca2+]i. Blockade of voltage-sensitive calcium channels (VSCC) with either verapamil (5·10-6 M) or nifedipine (1·10-6 M) completely abolished the effect of BACL on [Ca2+]i. In the presence of 12.5 mM potassium concentration baclofen significantly inhibited [Ca2+]i. In conclusion, our results describe the negative coupling of adenohypophyseal GABAB receptors to VSCC through PTX-sensitive G-proteins. These characteristics suggest a resemblance of these receptors to the typical presynaptic GABAB sites described in the central nervous system. Copyright © 2001 S. Karger AG, Basel. 2001 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v73_n5_p334_LuxLantos http://hdl.handle.net/20.500.12110/paper_00283835_v73_n5_p334_LuxLantos
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Calcium
Cyclic AMP
G proteins
GABAB receptors
Gamma-aminobutyric acid
Gamma-aminobutyric acid receptors
Gonadotropin-releasing hormone
Gonadotropins
Prolactin
Thyrotropin-releasing hormone
2 hydroxysaclofen
4 aminobutyric acid B receptor
4 aminobutyric acid B receptor blocking agent
baclofen
barium
calcium channel
calcium ion
cyclic AMP
dopamine
forskolin
fura 2 acetoxymethyl ester
gonadorelin
guanine nucleotide binding protein
hypophysis hormone
luteinizing hormone
nifedipine
pertussis toxin
potassium channel blocking agent
prolactin
protirelin
tetrylammonium
trypsin
verapamil
adenohypophysis
animal cell
animal tissue
article
calcium cell level
controlled study
female
hypophysis cell
luteinizing hormone release
nonhuman
presynaptic nerve
priority journal
proestrus
prolactin release
rat
receptor binding
Animals
Baclofen
Barium Compounds
Calcium
Calcium Channel Blockers
Cells, Cultured
Chlorides
Cyclic AMP
Dopamine
Female
Forskolin
Luteinizing Hormone
Pertussis Toxin
Pituitary Gland, Anterior
Potassium Channel Blockers
Potassium Chloride
Proestrus
Prolactin
Rats
Receptors, GABA-B
Tetraethylammonium
Thyrotropin-Releasing Hormone
Virulence Factors, Bordetella
spellingShingle Calcium
Cyclic AMP
G proteins
GABAB receptors
Gamma-aminobutyric acid
Gamma-aminobutyric acid receptors
Gonadotropin-releasing hormone
Gonadotropins
Prolactin
Thyrotropin-releasing hormone
2 hydroxysaclofen
4 aminobutyric acid B receptor
4 aminobutyric acid B receptor blocking agent
baclofen
barium
calcium channel
calcium ion
cyclic AMP
dopamine
forskolin
fura 2 acetoxymethyl ester
gonadorelin
guanine nucleotide binding protein
hypophysis hormone
luteinizing hormone
nifedipine
pertussis toxin
potassium channel blocking agent
prolactin
protirelin
tetrylammonium
trypsin
verapamil
adenohypophysis
animal cell
animal tissue
article
calcium cell level
controlled study
female
hypophysis cell
luteinizing hormone release
nonhuman
presynaptic nerve
priority journal
proestrus
prolactin release
rat
receptor binding
Animals
Baclofen
Barium Compounds
Calcium
Calcium Channel Blockers
Cells, Cultured
Chlorides
Cyclic AMP
Dopamine
Female
Forskolin
Luteinizing Hormone
Pertussis Toxin
Pituitary Gland, Anterior
Potassium Channel Blockers
Potassium Chloride
Proestrus
Prolactin
Rats
Receptors, GABA-B
Tetraethylammonium
Thyrotropin-Releasing Hormone
Virulence Factors, Bordetella
GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects
topic_facet Calcium
Cyclic AMP
G proteins
GABAB receptors
Gamma-aminobutyric acid
Gamma-aminobutyric acid receptors
Gonadotropin-releasing hormone
Gonadotropins
Prolactin
Thyrotropin-releasing hormone
2 hydroxysaclofen
4 aminobutyric acid B receptor
4 aminobutyric acid B receptor blocking agent
baclofen
barium
calcium channel
calcium ion
cyclic AMP
dopamine
forskolin
fura 2 acetoxymethyl ester
gonadorelin
guanine nucleotide binding protein
hypophysis hormone
luteinizing hormone
nifedipine
pertussis toxin
potassium channel blocking agent
prolactin
protirelin
tetrylammonium
trypsin
verapamil
adenohypophysis
animal cell
animal tissue
article
calcium cell level
controlled study
female
hypophysis cell
luteinizing hormone release
nonhuman
presynaptic nerve
priority journal
proestrus
prolactin release
rat
receptor binding
Animals
Baclofen
Barium Compounds
Calcium
Calcium Channel Blockers
Cells, Cultured
Chlorides
Cyclic AMP
Dopamine
Female
Forskolin
Luteinizing Hormone
Pertussis Toxin
Pituitary Gland, Anterior
Potassium Channel Blockers
Potassium Chloride
Proestrus
Prolactin
Rats
Receptors, GABA-B
Tetraethylammonium
Thyrotropin-Releasing Hormone
Virulence Factors, Bordetella
description The activation of pituitary GABAB receptors by the specific agonist baclofen inhibits pituitary hormone secretion in vitro. Here we studied the mechanism of action of GABAB receptors in rat adenohypophysis. Anterior pituitary cells were obtained by trypsinization and were either plated for hormonal studies and cAMP determination or incubated in FURA 2AM for calcium measurements. Baclofen (BACL: 1·10-5 M) significantly inhibited basal and thyrotropic releasing hormone (TRH)-stimulated (1·10-7 M) PRL secretion in anterior pituitary cells from proestrous rats. In the presence of pertussis toxin (PTX: 150 ng/ml, 20 h), which leads to the uncoupling of the Gi/o-protein from the receptor, both effects of BACL were abolished while the effect of dopamine (DA: 1·10-8 M), used as an inhibitory control, was reduced from 70 to 25%. PTX also reversed BACL-induced inhibition of gonadotropin-releasing hormone (GnRH)-elicited luteinizing hormone (LH) secretion in anterior pituitary cells from 15-day-old female rats. In addition, though working in a pituitary mixed cell population, in which only some cell types possess GABAB receptors, BACL (1·10-5 M) attenuated the forskolin-induced (0.5 μM) increase in cAMP. This effect was prevented by co-incubation with the antagonist 2 hydroxysaclofen and by preincubation with PTX. BACL (5·10-5 M) and DA (5·10-7 M) inhibited basal intracellular calcium concentrations ([Ca2+]i) in pituitary cells and the effect of the latter was significantly stronger. The effect of BACL on [Ca2+]i was abolished after preincubation with PTX. In the presence of the potassium channel blocking agents barium (200 μM and 1 mM) and tetraethylammonium (10 mM), BACL was still able to inhibit [Ca2+]i. Blockade of voltage-sensitive calcium channels (VSCC) with either verapamil (5·10-6 M) or nifedipine (1·10-6 M) completely abolished the effect of BACL on [Ca2+]i. In the presence of 12.5 mM potassium concentration baclofen significantly inhibited [Ca2+]i. In conclusion, our results describe the negative coupling of adenohypophyseal GABAB receptors to VSCC through PTX-sensitive G-proteins. These characteristics suggest a resemblance of these receptors to the typical presynaptic GABAB sites described in the central nervous system. Copyright © 2001 S. Karger AG, Basel.
title GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects
title_short GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects
title_full GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects
title_fullStr GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects
title_full_unstemmed GABAB receptors in anterior pituitary cells: Mechanism of action coupled to endocrine effects
title_sort gabab receptors in anterior pituitary cells: mechanism of action coupled to endocrine effects
publishDate 2001
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v73_n5_p334_LuxLantos
http://hdl.handle.net/20.500.12110/paper_00283835_v73_n5_p334_LuxLantos
_version_ 1768543265366212608