The role of phospholipase in reduced beta-adrenergic responsiveness in experimental asthma.
This investigation was designed to elucidate the role of phospholipase (PLase) in relation to reduced beta-adrenergic responsiveness in guinea pigs subjected to experimental asthma. In the in vivo experiment, guinea pigs that had developed asthma-like symptoms after exposure to an aerosol of 2% ovalbumin for 7 to 8 min for 10 successive days were used as the experimental asthma group. The control group was exposed to saline. The endogenous PLase activity was determined by high performance liquid chromatography using ditridecanoyl phosphatidylcholine as a substrate. PLase activity of lung membranes in the experimental asthma group was significantly elevated by 50% compared with that in the control group. Phospholipid content of lung membranes in the experimental asthma group was decreased by 11% compared with that in the control group. The experimental asthma group showed a 37% decrease in the number of beta-adrenoceptors in lung membranes and a 54% decrease in isoproterenol-stimulated adenylate cyclase activity in lung membranes compared with the control group. Although forskolin-stimulated adenylate cyclase activity was also reduced by 24%, decreases in forskolin-stimulated activity were less than decreases in isoproterenol-stimulated activity. In the in vitro experiment phospholipids in lung membranes were degraded by pretreatment with 0.1 U of PLase A2. After pretreatment of lung membranes with PLase A2, the number of beta-adrenoceptors was reduced by 25% compared with that in the control group, and adenylate cyclase activity stimulated by isoproterenol and forskolin were also reduced by 67 and 28%, respectively. PLase A2 had a minor effect on forskolin-stimulated activity as compared with isoproterenol-stimulated activity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000503:physiopathology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D005227:Fatty Acids; D008565:Membrane Proteins; D010743:Phospholipids; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D010740:Phospholipases; D010741:Phospholipases A; D000262:Adenylyl Cyclases; D007545:Isoproterenol