Abstract
It has been proposed that mastoparan (INLKALAALAKKIL) and other mast cell secretagogues such as substance P (SP) or compound 48/80 act by direct activation of the pertussis toxin (PTX)-sensitive G-proteins in intact cells. Here we have investigated whether or not the antagonists of SP, [D-Trp7, 9, 10] SP1-11 and [D-Trp7, 9, 10, N-leu11] SP1-11, can similarly induce exocytosis from RINm5F cells. In intact cells mastoparan and the SP antagonists stimulated insulin release in a dose-dependent manner at concentrations ranging from 10 to 100 µM. The maximal effect on insulin release, of both mastoparan and the SP antagonists was comparable to that obtained with 100 µM forskolin. Pretreatment of the intact cells, for 18 h with PTX or 6 h with cholera toxin, did not change the responses induced by both mastoparan and the SP antagonists. This absence of PTX effect, despite the fact that the three PTX substrates at 41, 40 and 39 kDa were ADP ribosylated after pretreatment suggests intrinsic differences between mast and RINm5F cells. Thus the SP antagonists behave similarly to mastoparan in its ability to induce insulin release in RINm5F cells. However, the higher concentrations required with RINm5F cells compared to that needed for mast cells suggest differences either in G-proteins composition or in the phospholipid composition of the membranes.
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Abbreviations
- SP-Substance P:
-
SPa:[d-Trp7, 9, 10] SP1−11, SPb:[D-Trp7, 9, 10, N-leu11]SP1−11
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Hillaire-Buys, D., Mousli, M., Landry, Y. et al. Insulin releasing effects of mastoparan and amphiphilic substance P receptor antagonists on RINm5F insulinoma cells. Mol Cell Biochem 109, 133–138 (1992). https://doi.org/10.1007/BF00229767
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DOI: https://doi.org/10.1007/BF00229767