Constitutive and basal secretion from the endocrine cell line, AtT-20

If constitutive secretion of trypsinogen and r chain has a half time of •1 h, as the data from the variant show, the slow unstimulated release of trypsinogen from wild type cells (Fig. 4 ,4) must have another explanation. One possibility is that unstimulated release in wild type cells is not due entirely to constitutive secretion but also because of basal release. Basal release is secretion from the regulated pathway in the absence of prior stimulation with a secretagogue. If a secreted prohormone is processed to its mature form after sorting into the regulated pathway (Orci et al., 1987b) , then basal release will appear as the unstimulated release of mature hormone. When the secretion of insulin forms was examined in wild type cells (Fig. 4 C) , mature insulin was indeed released in the absence of stimulation. During the chase, the rate of [35S]labeled insulin secretion dropped with a half life of,'o 3 h, while the rate of proinsulin secretion fell with a half time of only 40 rain. The kinetics suggest that mature insulin is released basally from secretory granules and proinsulin from the constitutive pathway. Consistent with this explanation is the observation that whereas exposure to 8-Br-cAMP increased the rate of insulin secretion sevenfold, it had no effect on the rate of proinsulin secretion. Proinsulin-transfected HYA.15.6 variant cells secreted proinsulin and neither stored it nor processed the prohormone to the mature form (data not shown). Comparison of the variant and wild type cells clearly demonstrates therefore, two forms of unstimulated release, constitutive and basal.