Inhibition of pituitary hormone exocytosis by a synthetic peptide related to the rab effector domain.
GTP-binding proteins of the rab family are believed to function at several steps in intracellular vesicular transport. We examined the effects of a rab-related peptide in permeabilized pituitary cells, in which exocytosis can be triggered by distinct Ca(2+)-dependent or Ca(2+)-independent pathways. We report that a synthetic peptide of 18 amino acids related to the rab effector domain, rab3AL (30-47) inhibited luteinizing hormone (LH) and growth hormone (GH) exocytosis triggered by either pathway. Ca(2+)-stimulated LH and GH release were inhibited by more than 80% and 50%, respectively, by 100 microM peptide. The peptide (100 microM) also inhibited LH and GH exocytosis stimulated by phorbol myristate acetate plus cAMP by more than 45% and 80%, respectively. The effect was sequence-specific since a second peptide, lacking the first 3 amino acids but otherwise identical failed to inhibit exocytosis. These results suggest that a protein of the rab family is involved in regulated pituitary hormone exocytosis, and they identify 3 amino acids of the putative rab effector domain which may be functionally important in exocytosis.
Department of Chemical Pathology, University of Cape Town Medical School, South Africa.
J S
JS
Davidson
A
A
Eales
R W
RW
Roeske
R P
RP
Millar
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D019204:GTP-Binding Proteins; D013006:Growth Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010907:Pituitary Hormones / Q000378:metabolism*; D012756:Sheep; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020692:rab3 GTP-Binding Proteins
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010907:Pituitary Hormones; D007986:Luteinizing Hormone; D013006:Growth Hormone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium