Cytochalasin B and Release of Growth Hormone

Abstract

MICROTUBULES are believed to be involved in emiocytosis, in which secretory granules migrate and fuse with the cell membrane, thereby liberating the granule contents into the extracellular space. Important evidence for this is that the release of insulin from pancreatic islets of Langerhans^1,2, histamine from mast cells³ and from leucocytes⁴, and catecholamines from the adrenal medulla⁵ is inhibited by colchicine, which, at lower concentrations, disrupts microtubular systems⁶. Although the function of microtubules in the secretory process is far from clear, it has been postulated that they are part of a contractile system which could move granules to the cell surface, or could be involved in the final release mechanism⁵. If contractile proteins do play a fundamental part in secretion in the four systems investigated, they would also be expected to be involved in other secretory systems. However, stimulation of growth hormone release in vitro is inhibited by colchicine only at the high concentration of 5 mM, at which concentration basal release is doubled by the drug⁷. This relative insensitivity to colchicine could be reconciled with an involvement of contractile proteins in secretion if microfilaments, rather than microtubules, were important in the release of growth hormone. Microfilaments are not affected by treatment with colchicine⁸ but may be disrupted by cytochalasin B⁹, and the effect of this drug on in vitro secretion of ox growth hormone in response to Ba²⁺, high extracellular K⁺, and prostaglandin E₂ has therefore been tested.