Membrane-association and the sensitivity of guanylyl cyclase-coupled receptors to nitric oxide.
Nitric oxide (NO) signal transduction occurs through guanylyl cyclase-coupled receptors, which exist in both cytosolic and membranous locations. It has recently been reported from experiments using heart tissue that the membrane-associated receptor has enhanced sensitivity to NO. Owing to its potential importance, we tested this finding using a method of applying NO in known, constant concentrations. The results showed that the concentration-response curves for receptor activation in cytosolic and membrane preparations of two different tissues (cerebellum and platelets) were indistinguishable. In all cases, half-maximal activation required about 1 nM NO and the curves had Hill coefficients of close to 1. The differential sensitivity reported for the heart is attributed to NO being scavenged by myoglobin in the cytosol, but not in the membrane fraction.
Wykes
Victoria
V
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT.
Garthwaite
John
J
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004048:Diethylamines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006162:Guanylate Cyclase / Q000187:drug effects* / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009211:Myoglobin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004048:Diethylamines; D009211:Myoglobin; D011956:Receptors, Cell Surface; D009569:Nitric Oxide; C034281:diethylamine; D006162:Guanylate Cyclase