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Melittin potentiates guanylate cyclase activation stimulated by atrial natriuretic factor and ATP
The biologically relevant receptor for atrial natriuretic factor (ANF) has been shown to be membrane-bound guanylate cyclase. While guanylate cyclase is known to be activated by ANF and ATP, the molecular mechanism of the enzyme activation remains unclear. We now show that melittin, the main peptide...
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Published in: | The Journal of biological chemistry 1993-03, Vol.268 (7), p.4908-4911 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The biologically relevant receptor for atrial natriuretic factor (ANF) has been shown to be membrane-bound guanylate cyclase.
While guanylate cyclase is known to be activated by ANF and ATP, the molecular mechanism of the enzyme activation remains
unclear. We now show that melittin, the main peptide toxin of bee venom, activates membrane-bound guanylate cyclase and potentiates
ANF- and ATP-stimulated guanylate cyclase activity in rat lung membranes. Melittin stimulated basal guanylate cyclase activity
by increasing the Vmax without significantly affecting the Km of the substrate, GTP. However, melittin enhances ANF- and ATP-stimulated
enzyme activity by altering both the Vmax and the EC50 of ANF and ATP. Although melittin activates guanylate cyclase in crude
membranes, it has little effect on the activity of the purified enzyme. The effect of melittin on guanylate cyclase activation
in rat lung membranes is attenuated by the Ca2+ chelator, EGTA. These results suggest that the effects of melittin on guanylate
cyclase activation may require the participation of accessory proteins or nonprotein factors. Therefore, melittin would be
a valuable tool for exploring the molecular mechanisms of ANF-mediated guanylate cyclase activation. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)53481-5 |