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The Journal of Neuroscience, September 15, 1999, 19(18):7721-7731
Expression of Ca2+-Mobilizing EndothelinA
Receptors and Their Role in the Control of Ca2+ Influx and
Growth Hormone Secretion in Pituitary Somatotrophs
Melanija
Tomi ,
Dragoslava
Zivadinovic,
Fredrick
Van Goor,
Davy
Yuan,
Taka-aki
Koshimizu, and
Stanko S.
Stojilkovic
Endocrinology and Reproduction Research Branch, National Institute
of Child Health and Human Development, National Institutes of Health,
Bethesda, Maryland 20892
The expression and coupling of endothelin (ET) receptors were
studied in rat pituitary somatotrophs. These cells exhibited periods of
spontaneous action potential firing that generated high-amplitude
fluctuations in cytosolic calcium concentration ([Ca2+]i). The message and the
specific binding sites for ETA, but not ETB, receptors were found in mixed pituitary cells
and in highly purified somatotrophs. The activation of these receptors
by ET-1 led to an increase in inositol 1,4,5-trisphosphate production and the associated rise in [Ca2+]i and
growth hormone (GH) secretion. The Ca2+-mobilizing
action of ET-1 lasted for 2-3 min and was followed by an inhibition of
action potential-driven Ca2+ influx and GH secretion
to below the basal levels. As in somatostatin-treated cells, the
ET-1-induced inhibition of spontaneous electrical activity and
Ca2+ influx was accompanied by the inhibition of
adenylyl cyclase and by the stimulation of inward rectifier potassium
current. In contrast to somatostatin, ET-1 did not inhibit
voltage-gated Ca2+ channels. During prolonged
agonist stimulation a gradual recovery of Ca2+
influx and GH secretion occurred. In somatotrophs treated with pertussis toxin overnight, the ET-1-induced
Ca2+-mobilizing phase was preserved, but it was
followed immediately by facilitated Ca2+
influx and GH secretion. Both somatostatin- and ET-1-induced inhibitions of adenylyl cyclase activity were abolished in pertussis toxin-treated cells. These results indicate that the transient cross-coupling of Ca2+-mobilizing ETA
receptors to the Gi/Go pathway in
somatotrophs provides an effective mechanism to change the rhythm of
[Ca2+]i signaling and GH secretion
during continuous agonist stimulation.
Key words:
somatotrophs; growth hormone; calcium; endothelin; somatostatin; electrical activity
Copyright © 1999 Society for Neuroscience 0270-6474/99/19187721-11$05.00/0
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