The endocrine secretion granule revisited— Postulating new functions

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The traditional functions of the secretion vesicle are the intracellular storage and transport of secretory products. However, the endocrine secretion vesicle may contain factors or elements which not only passively promote the secretory process but which may play an active role in the regulation of hormone secretion. Secretion vesicles have been demonstrated to contain binding sites for various peptide hormones including GnRH and somatostatin. Secretion vesicle migration and concomitantly, intracellular transport of receptors from the Golgi apparatus to the cell surface can be accelerated by various secretagogues. Glucose (300 mg/dl) and tolbutamide both stimulate insulin release and the recruitment of somatostatin receptors. Alternatively, agents (colchicine and D 2O) which interfere with secretion vesicle migration appear to specifically suppress the recruitment of somatostatin receptors to the plasma membrane. The greatest proportion (87%) of the total cellular pool of somatostatin receptors is located intracellularly. Upon glucose stimulation, secretion vesicles translocate 8%–10% of these intracellular receptors to the surface membrane. If the thesis is correct concerning the role of the secretion vesicle in the transport of somatostatin receptors to the cell surface, then the recruitment of somatostatin receptors may provide a useful marker for determining the event of granule fusion to the plasma membrane. Sodium isethionate which suppresses osmotic lysis of granules blocks glucose-induced insulin release from isolated islets but not the recruitment of somatostatin receptors. In various endocrine tissues, the secretion vesicles have been shown to contain adenine nucleotides in a proportion differing from other subcellular organelles. The secretion vesicle pool of adenine nucleotides is not readily exchangeable with the remainder of the cell. It can be demonstrated that the isolated secretion vesicle fraction possesses the capacity to convert ATP into other adenine nucleotides. Furthermore, it is evident that secretion vesicles isolated from the anterior pituitary gland and pancreatic islets possess cyclic AMP stimulated protein kinase activity. Controversy exists concerning the site of action of somatostatin in suppressing hormone release. While certain studies have demonstrated an effect of somatostatin in inhibiting the generation of cyclic AMP, other investigators have suggested that somatostatin acts distal to this step, perhaps interfering with protein phosphorylation, i.e. an effect on cyclic AMP dependent protein kinase or phosphoprotein phosphatase. Somatostatin appears to inhibit cyclic AMP induced protein phosphorylation in secretion vesicles isolated from the islets and the anterior pituitary gland. There is no effect of somatostatin in inhibiting cyclic AMP stimulated protein phosphorylation in isolated pituitary plasma membranes. It is suggested that during exocytosis, the secretion vesicles may transfer to the plasma membrane both the receptor and effector units for somatostatin action. While the secretion vesicles appear to be relatively rich in Ca ++, whether or not they play an active role in intracellular translocation of calcium remains to be established. It is conceivable that the high concentration of calcium in the secretion vesicle serves some role, although as yet, this has not been defined. In summary, the role of the secretion vesicle in hormone secretion is multifaceted, encompassing storage and transport of secretory products, translocation of receptors for agonistic and antagonistic agents and possessing an effector unit which has the capability of modifying hormone release.