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Somatostatin‐14 Actions on Dopamine‐ and Pituitary Adenylate Cyclase‐Activating Polypeptide‐Evoked Ca 2+ Signals and Growth Hormone Secretion
Author(s) -
Yunker W. K.,
Chang J. P.
Publication year - 2004
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2004.01218.x
Subject(s) - endocrinology , medicine , somatostatin , adenylate kinase , dopamine , secretion , cyclase , chemistry , anterior pituitary , hormone , pituitary gland , biology , stimulation , receptor
Using single‐cell Ca 2+ imaging and a growth hormone (GH) radioimmunassay, we investigated somatostatin‐14 (SS 14 ) inhibition of cAMP‐dependent, stimulated GH secretion from primary cultures of dispersed goldfish pituitary cells. The dopamine‐D1 receptor agonist SKF‐38393, and the hypothalamic neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP) both elevated intracellular Ca 2+ concentration ([Ca 2+ ] i ) and stimulated GH release. When increases in [Ca 2+ ] i were prevented by intracellular loading of BAPTA, a Ca 2+ chelator, SKF‐38393‐ and PACAP‐stimulated GH release were inhibited, suggesting that these Ca 2+ signals are required for stimulated GH release. SS 14 inhibited SKF‐38393‐ and PACAP‐stimulated GH release, but did not prevent these Ca 2+ signals. Kinetic analysis revealed that SS 14 lowered the maximum amplitude of the SKF‐38393‐ and PACAP‐evoked Ca 2+ responses, but had no effect on other aspects of the Ca 2+ signal. We then examined the ability of SS 14 to act subsequent to dopamine‐D1 or PACAP receptor activation using the adenylate cyclase activator forskolin, or the membrane permeant cAMP analogue 8Br‐cAMP. Forskolin and 8Br‐cAMP both increased [Ca 2+ ] i and GH secretion and, as expected, SS 14 inhibited the resultant GH release. Although SS 14 significantly increased the time to maximum amplitude of the forskolin‐evoked Ca 2+ signals, it had no detectable effect on any of the kinetic parameters used to describe the Ca 2+ signals evoked by 8Br‐cAMP. Taken together, these results establish that SS 14 has the ability to suppress Ca 2+ ‐dependent exocytosis by acting distal to elevations in [Ca 2+ ] i . Furthermore, it appears likely that the cellular mechanisms underlying the observed effects of SS 14 on Ca 2+ signalling are upstream of cAMP and may be unrelated to those responsible for inhibiting GH release.