Biomaterial Database

Melittin potentiates guanylate cyclase activation stimulated by atrial natriuretic factor and ATP. 1993

C H Chang, and D L Song

Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.

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.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008297	Male		Males
D008555	Melitten	Basic polypeptide from the venom of the honey bee (Apis mellifera). It contains 26 amino acids, has cytolytic properties, causes contracture of muscle, releases histamine, and disrupts surface tension, probably due to lysis of cell and mitochondrial membranes.	Melittin,Mellitin
D009320	Atrial Natriuretic Factor	A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.	ANF,ANP,Atrial Natriuretic Peptide,Atrial Natriuretic Peptides,Atriopeptins,Auriculin,Natriuretic Peptides, Atrial,ANF (1-126),ANF (1-28),ANF (99-126),ANF Precursors,ANP (1-126),ANP (1-28),ANP Prohormone (99-126),ANP-(99-126),Atrial Natriuretic Factor (1-126),Atrial Natriuretic Factor (1-28),Atrial Natriuretic Factor (99-126),Atrial Natriuretic Factor Precursors,Atrial Natriuretic Factor Prohormone,Atrial Natriuretic Peptide (1-126),Atrial Pronatriodilatin,Atriopeptigen,Atriopeptin (1-28),Atriopeptin (99-126),Atriopeptin 126,Atriopeptin Prohormone (1-126),Cardiodilatin (99-126),Cardiodilatin Precursor,Cardionatrin I,Cardionatrin IV,Prepro-ANP,Prepro-CDD-ANF,Prepro-Cardiodilatin-Atrial Natriuretic Factor,Pro-ANF,ProANF,Proatrial Natriuretic Factor,Pronatriodilatin,alpha ANP,alpha-ANP Dimer,alpha-Atrial Natriuretic Peptide,beta-ANP,beta-Atrial Natriuretic Peptide,gamma ANP (99-126),gamma-Atrial Natriuretic Peptide,Natriuretic Peptide, Atrial,Peptide, Atrial Natriuretic,Peptides, Atrial Natriuretic,Prepro ANP,Prepro CDD ANF,Prepro Cardiodilatin Atrial Natriuretic Factor,Pro ANF,alpha ANP Dimer,alpha Atrial Natriuretic Peptide,beta ANP,beta Atrial Natriuretic Peptide,gamma Atrial Natriuretic Peptide
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006162	Guanylate Cyclase	An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.	Guanyl Cyclase,Deoxyguanylate Cyclase,Guanylyl Cyclase,Inosinate Cyclase,Cyclase, Deoxyguanylate,Cyclase, Guanyl,Cyclase, Guanylate,Cyclase, Guanylyl,Cyclase, Inosinate