Direct and indirect receptor-independent G-protein activation by cationic-amphiphilic substances. Studies with mast cells, HL-60 human leukemic cells and purified G-proteins
- PMID: 8528595
- DOI: 10.1111/j.1600-0625.1995.tb00251.x
Direct and indirect receptor-independent G-protein activation by cationic-amphiphilic substances. Studies with mast cells, HL-60 human leukemic cells and purified G-proteins
Abstract
Studies from several laboratories have revealed that structurally diverse substances including the wasp venom, mastoparan (MP), activate purified regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins) in a receptor-independent manner, presumably by mimicking the effects of heptahelical receptors. Mast cells and differentiated HL-60 human leukemic cells are useful model systems for the analysis of receptor-independent G-protein activation. We compared the effects of 2-phenylhistamines which are cationic-amphiphilic, too, and of MP on G-protein activation in dibutyryl cAMP-differentiated HL-60 cells and in the rat basophilic leukemia cell line, RBL 2H3. In HL-60 cells, 2-phenylhistamines show stimulatory effects which resemble those of formyl peptide receptor agonists but which cannot be attributed to agonism at classical receptors. 2-phenylhistamines do not, however, activate RBL 2H3 cells and various other myeloid cell types, pointing to cell type-specificity of receptor-independent G-protein activation. In HL-60 cells, MP shows effects on G-protein activation which differ substantially from those of formyl peptides. In RBL 2H3 membranes, MP shows similar effects on G-protein activation as in HL-60 membranes. We develop a model according to which receptor-independent G-protein activation can be subdivided into direct and indirect receptor-independent G-protein activation. In case of the former mechanism, substances like 2-phenylhistamines interact with G-protein alpha-subunits and in case of the latter mechanism, substances like MP interact with nucleoside diphosphate kinase which catalyzes the formation of GTP. This newly formed GTP is then transferred to, and cleaved by, G-protein alpha-subunits.(ABSTRACT TRUNCATED AT 250 WORDS)
Similar articles
-
Activation of GTP formation and high-affinity GTP hydrolysis by mastoparan in various cell membranes. G-protein activation via nucleoside diphosphate kinase, a possible general mechanism of mastoparan action.Biochem Pharmacol. 1996 Feb 9;51(3):217-23. doi: 10.1016/0006-2952(95)02119-1. Biochem Pharmacol. 1996. PMID: 8573186
-
Receptor-independent G protein activation may account for the stimulatory effects of first-generation H1-receptor antagonists in HL-60 cells, basophils, and mast cells.Biochem Pharmacol. 1996 Jan 26;51(2):125-31. doi: 10.1016/0006-2952(95)02123-x. Biochem Pharmacol. 1996. PMID: 8615880
-
Mastoparan may activate GTP hydrolysis by Gi-proteins in HL-60 membranes indirectly through interaction with nucleoside diphosphate kinase.Biochem J. 1994 Dec 1;304 ( Pt 2)(Pt 2):377-83. doi: 10.1042/bj3040377. Biochem J. 1994. PMID: 7998971 Free PMC article.
-
G-protein-coupled receptors in HL-60 human leukemia cells.Gen Pharmacol. 1996 Jan;27(1):33-54. doi: 10.1016/0306-3623(95)00107-7. Gen Pharmacol. 1996. PMID: 8742493 Review.
-
G protein activation: a receptor-independent mode of action for cationic amphiphilic neuropeptides and venom peptides.Trends Pharmacol Sci. 1990 Sep;11(9):358-62. doi: 10.1016/0165-6147(90)90179-c. Trends Pharmacol Sci. 1990. PMID: 2122563 Review.
Cited by
-
Hypothesized and found mechanisms for potentiation of bradykinin actions.Signal Transduct. 2006 Feb;6(1):5-18. doi: 10.1002/sita.200500061. Epub 2006 Jan 17. Signal Transduct. 2006. PMID: 32327962 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources