Assessment of signal transduction mechanisms regulating airway smooth muscle contractility.
Agonist-receptor interactions regulate airway smooth muscle tone through activation of guanine nucleotide binding proteins (G proteins) which are coupled to second-messenger pathways that mediate changes in the tissue's contractile state. Various methods have been applied to identify the structure/function characteristics of G proteins and their role in signal transduction in airway smooth muscle, including the use of exotoxins, nonhydrolyzable analogs of guanosine-triphosphate (GTP), antibodies to purified G proteins, and membrane reconstitution studies. In elucidating mechanisms of airway smooth muscle relaxation, considerable progress has been made in identifying the molecular basis for receptor/G protein coupling and other regulatory processes leading to both the activation and down-regulation of the adenylate cyclase/adenosine 3',5'-cyclic monophosphate system. Further, with respect to airway smooth muscle contraction, various approaches have been used to evaluate the role of membrane phosphoinositide turnover and the mechanisms of action of the bifurcating signal transduction pathways associated with the production and metabolism of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol, and activation of protein kinase C. This review identifies much of the information gained to date on the above signal transduction pathways, with an emphasis placed on various methodological approaches used to determine membrane and transmembrane signaling processes in airway smooth muscle.
Schramm
C M
CM
Division of Pulmonary Medicine, Joseph Stokes, Jr., Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania, School of Medicine 19104.
Grunstein
M M
MM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010716:Phosphatidylinositols / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology
D010716:Phosphatidylinositols; D000242:Cyclic AMP; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases