Interleukin-1[alpha] stimulates dopamine release by activating type ii protein kinase a in pc-12 cells 1. Mendrinos, Alexandra, A. Kumar, Nancy A. O'connell, R. K. Agarwal, and Andrea R. Gwosdow. Endocrine Unit, Massachusetts General Hospital, Harvard Medical School and Shriners Burns Institute, Boston, MA and Tufts University School of Veterinary Medicine, Grafton, MA
APStracts 2:0149E, 1995.
A recent study from this laboratory (12) has shown that the inflammatory mediator, interleukin-1[alpha] (IL-1[alpha]), stimulates catecholamine release from primary cultures of rat adrenal cells. This adrenal cell preparation contained adrenal medullary cells (22). To study the actions of IL-1[alpha] on the adrenal medulla, the adrenal medullary cell line, PC-12, was used. PC-12 cells secrete dopamine as the primary catecholamine. The present studies were conducted to determine a) if IL-1[alpha] stimulates dopamine release, and b) if the cAMP-PKA pathway is involved in IL-1[alpha]-induced dopamine release from PC-12 cells. The results indicate that IL -1[alpha] significantly (P&LT0.05) elevated dopamine release after a 24 hr incubation period. IL-1[alpha] did not stimulate cAMP accumulation at any time period between 5 min and 2 hr. In contrast, forskolin-treated cells elevated (P&LT0.05) intracellular cAMP levels and increased dopamine release. Because IL-1[alpha] did not affect cAMP accumulation, the effect of IL-1[alpha] on PKA activity was investigated. IL-1[alpha] increased (P&LT0.05) PKA activity at 15 and 30 min and returned to control levels by 1 hr. Forskolin also increased (P &LT0.05) PKA activity. The type of PKA activated (P&LT0.05) by IL-1[alpha] was type II PKA. In contrast, forskolin activated (P&LT0.05) type I and type II PKA. Inhibition of PKA with the PKA inhibitor, H-8, blocked PKA activity and dopamine secretion by both IL-1[alpha] and forskolin in PC-12 cells. These observations demonstrate that a) IL-1[alpha] stimulated dopamine release from PC-12 cells by activating PKA, b) the mechanism of IL -1[alpha] activation of PKA does not involve detectable increases in intracellular cAMP accumulation and c) IL-1[alpha] activates type II PKA which is used by IL-1[alpha] to stimulate dopamine secretion from PC-12 cells. 

Received 7 March 1995; accepted in final form 29 June 1995.
APS Manuscript Number E104-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.