Abstract
Chinese hamster ovary (CHO) cells, stably transfected with the cloned rat CCK-A receptor, were used to study signal transduction events initiated by cholecystokinin octapeptide (CCK-8) and the partial agonist JMV-180. In single CHO-CCK-A cells loaded with fura-2, superfusion of CCK-8 (10 pM-1 nM) resulted in an increase in intracellular Ca2+ concentration ([Ca2+](i)). At CCK-8 concentrations <100 pM, the signal consisted of [Ca2+](i) oscillations. At higher concentrations, CCK-8 induced a typical biphasic response consisting of a large peak followed by a lower sustained plateau. Superfusion of JMV-180 also resulted in an increase in [Ca2+](i); in contrast to acinar cells this increase did not consist exclusively of [Ca2+](i) oscillations. Both CCK-8 and JMV-180 increased polyphosphoinositide hydrolysis, although JMV-180 stimulated formation of only 10% as much [3H]inositol phosphates. [Ca2+](i) signals stimulated by both CCK-8 and JMV-180 were blocked by the aminosteroid U-73122. CCK-8 (1-10 nM) increased formation of adenosine 3',5'-cyclic monophosphate (cAMP) and release of arachidonic acid in CHO-CCK cells. These increases were not mimicked by JMV-180 (10 μM). Furthermore, no cAMP formation or arachidonate release could be detected when cells were incubated with both JMV-180 and CCK-8. These data indicate that in CHO-CCK-A cells, unlike acinar cells, both CCK-8 and JMV-180 increase [Ca2+](i) by similar mechanisms. However, the CCK-A receptor can differentially recognize and then activate discrete transduction pathways on binding of these two agonists.
Original language | English (US) |
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Pages (from-to) | G999-G1004 |
Journal | AM.J.PHYSIOL. |
Volume | 265 |
Issue number | 5 28-5 |
DOIs | |
State | Published - 1993 |
Keywords
- Chinese hamster ovary cells
- cholecystokinin
- pancreatic acinar cells
- signal transduction
ASJC Scopus subject areas
- Physiology
- Gastroenterology