Inhibition of pituitary hormone exocytosis by a synthetic peptide related to the rab effector domain

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Abstract
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 Ca2+‐dependent or Ca2+‐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. Ca2+‐stimulated LH and GH release were inhibited by more than 80% and 50%, respectively, by 100 μM peptide. The peptide (100 μM) 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.