Dihydropyridine-sensitive calcium channel activity related to prolactin, growth hormone, and luteinizing hormone release from anterior pituitary cells in culture: interactions with somatostatin, dopamine, and estrogens.
In the present work, we determined the activity of voltage-dependent dihydropyridine (DHP)-sensitive Ca2+ channels related to PRL, GH, and LH secretion in primary cultures of pituitary cells from male or female rats. We investigated their modulation by 17 beta-estradiol (E2) and their involvement in dopamine (DA) and somatostatin (SRIF) inhibition of PRL and GH release. BAY-K-8644 (BAYK), a DHP agonist which increases the opening time of already activated channels, stimulated PRL and GH secretion in a dose-dependent manner. The effect was more pronounced on PRL than on GH release. BAYK-evoked hormone secretion was further amplified by simultaneous application of K+ (30 or 56 mM) to the cell cultures; in parallel, BAYK-induced 45Ca uptake by the cells was potentiated in the presence of depolarizing stimuli. In contrast, BAYK was unable to stimulate LH secretion from male pituitary cells, but it potentiated LHRH- as well as K+-induced LH release; it had only a weak effect on LH secretion from female cell cultures. Basal and BAYK-induced pituitary hormone release were blocked by the Ca2+ channel antagonist nitrendipine. Under no condition did BAYK affect the hydrolysis of phosphoinositides or cAMP formation. Pretreatment of female pituitary cell cultures with E2 (10(-9) M) for 72 h enhanced LH and PRL responses to BAYK, but was ineffective on GH secretion. DA (10(-7) M) inhibited basal and BAYK-induced PRL release from male or female pituitary cells treated or not treated with E2 (10(-9) M). SRIF (10(-9) and 10(-8) M) reversed BAYK-evoked GH release to the same extent in cell cultures derived from male or female animals. It was ineffective on BAYK-induced PRL secretion in the absence of E2, but antagonized it after E2 pretreatment. The effect was dependent upon the time of steroid treatment and was specific, since 17 alpha-estradiol was inactive. In addition, DA and SRIF decreased the 45Ca uptake induced by the calcium agonist. These data demonstrate that DHP-sensitive voltage-dependent calcium channels of the L type present on different pituitary cells are not equally susceptible to BAYK activation under steady state basal conditions, indicating that their spontaneous activity and/or distribution vary according to the cell type; their activity is modulated by sex steroids. In addition, these data suggest that Ca2+ channels represent a possible site of DA and SRIF inhibition of PRL and GH release, respectively, by gating calcium entry into the corresponding cells.
Drouva
S V
SV
U. 159 INSERM, Centre Paul Broca de l'INSERM, Paris, France.
Rerat
E
E
Bihoreau
C
C
Laplante
E
E
Rasolonjanahary
R
R
Clauser
H
H
Kordon
C
C
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002132:Calcium Radioisotopes / Q000378:metabolism; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013004:Somatostatin / Q000494:pharmacology*
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D004095:Dihydropyridines; D010908:Pituitary Hormones, Anterior; D004958:Estradiol; D013004:Somatostatin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D011388:Prolactin; D007986:Luteinizing Hormone; D013006:Growth Hormone; D009568:Nitrendipine; D011188:Potassium; D004298:Dopamine