RT Journal Article
SR Electronic
T1 Cellular mechanisms of somatostatin inhibition of calcium influx in the anterior pituitary cell line AtT-20.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 646
OP 651
VO 254
IS 2
A1 T Reisine
YR 1990
UL http://jpet.aspetjournals.org/content/254/2/646.abstract
AB The cellular mechanisms by which the hypothalamic peptide somatostatin (SRIF) inhibits Ca+(+) influx were investigated in the pituitary cell line AtT-20. Cytosolic Ca+(+) levels were measured using the fluorescent probe Quin 2. Calcium influx was stimulated by the Ca+(+) channel agonist Bay K 8644. Bay K 8644 increased Ca+(+) influx in a concentration-dependent manner and the stimulation of Ca+(+) influx was blocked by the Ca+(+) channel antagonists nifedipine and nitrendipine. SRIF analogs also blocked Bay K 8644-stimulated Ca+(+) influx. The rank order of potency of the analogs (SRIF-28 greater than D-Trp8-SRIF greater than SRIF) suggests that the effects of SRIF are mediated by SRIF-28 preferring receptors. Pretreatment of AtT-20 cells with pertussis toxin abolished SRIF's inhibition of Bay K 8644-evoked Ca+(+) influx suggesting that G proteins mediate the inhibitory effects of SRIF on Ca+(+) influx. The K+ channel antagonists tetraethylammonium, 4-aminopyridine and CsCl all stimulated Ca+(+) influx into AtT-20 cells. These agents did not alter Bay K 8644-evoked Ca+(+) influx or did they affect the ability of SRIF to inhibit Ca+(+) influx. Tetrodotoxin, the sodium channel blocker which inhibits action potential generation in AtT-20 cells, lowered basal Ca+(+) levels in AtT-20 cells but did not modify SRIF's inhibition of Bay K 8644-stimulated Ca+(+) influx. These findings suggest that SRIF receptors, linked directly to Ca+(+) channels via G proteins, may mediate SRIF's inhibition of Ca+(+) influx.