Phorbol diesters stimulate somatostatin secretion from cultured brain cells

Endocrinology
R A Peterfreund, W W Vale

Abstract

Phorbol diester tumor promoters are potent cocarcinogens which also possess activity in a variety of biological assays. We have examined the effect of phorbol diesters on secretion of somatostatin-like immunoactivity (SRIF-LI) by dispersed cells of fetal rat brain maintained in long term culture. Phorbol-12-myristate-13-acetate (PMA) and phorbol 12, 13-dibutyrate stimulate SRIF-LI secretion in a dose-dependent fashion. 4-O-Methyl-PMA is approximately 100 times less potent than phorbol 12, 13-dibutyrate. 4-beta-Phorbol was inactive. Treatment with a nonphorbol irritant, teleocidin, also was associated with significantly augmented release of SRIF-LI. Significant stimulation is seen within 7.5 min of treatment and response is linear over 1 h. Administration of phorbol diesters in low calcium buffer (0.1 mM) with or without cobalt or pretreatment with verapamil are associated with significantly diminished secretion. Substitution for sodium ion by choline or pretreatment with tetrodotoxin (10(-7) M) also inhibits response to PMA. gamma-Aminobutyric acid (50 microM) or the gamma-aminobutyric acid agonist muscimol (5 microM) decrease response to PMA as does sodium pentobarbital (IC50 approximately 30 microM). Phenobarbital is less pot...Continue Reading

Citations

Oct 1, 1985·Naunyn-Schmiedeberg's Archives of Pharmacology·A R WakadeT D Wakade
Nov 1, 1992·Brain Research Bulletin·L P KapcalaH H Juang
Jan 1, 1990·Critical Reviews in Clinical Laboratory Sciences·M ZaidiL H Breimer
Sep 1, 1984·The Journal of Allergy and Clinical Immunology·S A MetzR P Robertson
Feb 10, 1987·Brain Research·R C MalenkaR A Nicoll

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