Homologous desensitization of bombesin-induced increases in intracellular Ca2+ in quiescent swiss 3T3 cells involves a protein kinase C-independent mechanism
✍ Scribed by John H. Walsh; Mark Bouzyk; Enrique Rozengurt
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 856 KB
- Volume
- 156
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Addition of bombesin to Swiss 3T3 cells causes a rapid and transient increase in the intracellular concentration of Ca2+ ([Ca'+li), which is followed by desensitization to a subsequent addition of the peptide. The concentrations of bombesin used to study this acute cellular desensitization (0.1-0.5 nM) did not deplete the intracellular pool of Ca2+ released by inositol(l,4,5)trisphosphate, as shown by addition of vasopressin after consecutive additions of bombesin. Two lines of evidence support the conclusion that activation of protein kinase C (PKC) does not mediate the acute homologous desensitization of Ca2+ responses induced by bombesin. First, long-term treatment (48 h) of Swiss 3T3 cells with phorbol 12,13dibutyrate (PDB) to deplete PKC did not prevent homologous desensitization. The responses to second additions of bombesin at 0.1, 0.25, and 0.5 nM were 42%, 26% and 1 1 % of the initial responses, respectively. Second, the PKC inhibitor CF 109203X did not alter homologous desensitization at concentrations that completely prevented the inhibition of Ca2 + mobilization induced by PDB and blocked PDB-mediated phosphorylation of the prominent PKC substrate 80K/ MARCKS. We conclude that acute homologous desensitization of Ca'+ responses induced by bombesin occurs through a PKC-independent mechanism.