J. Biol. Chem., Vol. 261, Issue 20, 9105-9108, Jul, 1986
Participation of voltage-dependent calcium channels in the action of gonadotropin-releasing hormone
JP Chang, EE McCoy, J Graeter, K Tasaka and KJ Catt
The roles of calcium ions and voltage-sensitive calcium channels in
gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH)
release were investigated in rat anterior pituitary cells. The calcium
ionophores A23187 and ionomycin stimulated LH release from cultured
pituitary cells, in which ionomycin (5 X 10(-5) M) was as effective as a
maximal concentration of GnRH (10(-8) M). In addition, a concentration of
the calcium channel agonist methyl 1,4-dihydro-2,6-
dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate (BK
8644) (10(-8) M), which did not alter basal LH release, potentiated the
ability of submaximal (10(-10) and 10(-9) M) doses of GnRH to increase LH
secretion. Furthermore, concentrations of the calcium channel antagonist
nitrendipine (10(-8)-10(-5) M) that did not alter basal LH release,
inhibited GnRH-stimulated LH secretion by 30-40%. Nitrendipine (10(-8) M)
also blocked the potentiation of GnRH-induced LH secretion by BK 8644.
During column perifusion of pituitary cells, 10(-8) M nitrendipine reduced
the LH response to a 2-min pulse of 10(- 8) M GnRH by about 40%. In
Quin-2-loaded pituitary cells, supramaximal doses (10(-6) M) of a potent
GnRH agonist rapidly elevated cytoplasmic Ca2+ by 50-100 nM. Concomitant
treatment with nitrendipine decreased the GnRH agonist-induced Ca2+ signal
by 40-60%. These results indicate that increases in intracellular Ca2+ via
voltage-sensitive calcium channels partially reproduce GnRH action, and
also that GnRH causes activation of such channels. However, the increase in
cytoplasmic Ca2+ concentration during GnRH action must originate in part
from mobilization of internal Ca2+ stores, and its relatively small
magnitude may be consistent with the concomitant activation of protein
kinase C as an intermediate step in GnRH action.