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Synergistic actions of epidermal growth factor‐urogastrone and vasopressin in cultured aortic A‐10 smooth muscle cells
Author(s) -
Mokashi Shalini,
Severson David L.,
Hollenberg Morley D.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041520219
Subject(s) - epidermal growth factor , endocrinology , medicine , protein kinase c , diacylglycerol lipase , phospholipase c , biology , vascular smooth muscle , phospholipase a2 , arachidonic acid , diacylglycerol kinase , chemistry , phosphorylation , biochemistry , receptor , enzyme , smooth muscle
In cultured rat aorta‐derived A‐10 cells, epidermal growth factor‐urogastrone (EGF‐URO) acts synergistically with arginine vasopressin (AVP) to augment the AVP‐mediated release of 3 H‐arachidonate ( 3 H‐AA) from 3 H‐AA prelabeled cells. On its own, EGF‐URO had no effect on AA release and had no effect on calcium influx or efflux either in the absence or presence of AVP. The synergistic action of EGF‐URO was not affected by actinomycin D, cycloheximide, indomethacin, by the diacylglycerol lipase inhibitor U‐57, 908, or by the tyrosine kinase inhibitors genistein (GS) and tyrphostin (TP). TP did, nonetheless, completely abrogate 3 H‐thymidine incorporation triggered in the presence of EGF‐URO. Although EGF‐URO stimulated an increase in calpactin‐II (lipocortin‐I) phosphorylation in permeabilized cells, no such increase was detected in intact cells exposed to EGF‐URO either alone or in combination with AVP, under conditions where EGF‐URO augmented the action of AVP. The phospholipase A 2 inhibitor, mepacrine, had no effect on AVP‐mediated AA release, but abolished the synergistic action of EGF‐URO. We conclude that in contrast with our previous results with gastric smooth muscle strips, wherein EGF‐URO acts via the diacylglycerol lipasemediated metabolism of diacylglycerol, and in keeping with observations with cultured mesangial cells, EGF‐URO acts synergistically with AVP in A‐10 cells via the activation of phospholipase A 2 . This synergistic action of EGF‐URO does not appear to be due to increased levels of cyclooxygenase and would appear not to require increased tyrosine kinase activity. © 1992 Wiley‐Liss, Inc.