Quinidine and melittin both decrease the fluidity of liver plasma membranes and both inhibit hormone-stimulated...

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Adenylate cyclase is a key enzyme in cellular signaling pathways.
• Liver plasma membranes contain adenylate cyclase, regulated by hormones like glucagon.
• Membrane fluidity influences enzyme activity and drug interactions.

Purpose of the Study:

• To investigate the effects of quinidine and melittin on adenylate cyclase activity in liver plasma membranes.
• To determine the relationship between membrane order and enzyme inhibition by these agents.
• To explore the impact of quinidine and melittin on lipid phase behavior within the membrane.

Main Methods:

• Enzyme assays measuring glucagon- and fluoride-stimulated adenylate cyclase activity.
• Electron spin resonance (ESR) spectroscopy using a fatty acid probe (doxyl stearic acid) to assess membrane order.
• Analysis of Arrhenius plots to identify changes in enzyme kinetics and lipid phase transitions.

Main Results:

• Both quinidine and melittin inhibited adenylate cyclase activity in a dose-dependent manner.
• These agents increased liver plasma membrane order, correlating with quinidine's inhibition.
• Novel lipid phase separation at 12°C was observed with quinidine and melittin, affecting enzyme kinetics.

Conclusions:

• Increased membrane order contributes to quinidine's inhibition of adenylate cyclase.
• Melittin's inhibition is partly due to increased membrane order and a novel lipid phase separation.
• Quinidine and melittin induce distinct alterations in membrane lipid organization and enzyme activity.