Calcium sensitization produced by G protein activation in airway smooth muscle.
We determined whether activation of G proteins can affect the force developed for a given intracellular Ca(2+) concentration ([Ca(2+)]; i.e., the Ca(2+) sensitivity) by mechanisms in addition to changes in regulatory myosin light chain (rMLC) phosphorylation. Responses in alpha-toxin-permeabilized canine tracheal smooth muscle were determined with Ca(2+) alone or in the presence of ACh, endothelin-1 (ET-1), or aluminum fluoride (AlF; acute or 1-h exposure). Acute exposure to each compound increased Ca(2+) sensitivity without changing the response to high [Ca(2+)] (maximal force). However, chronic exposure to AlF, but not to chronic ACh or ET-1, increased maximal force by increasing the force produced for a given rMLC phosphorylation. Studies employing thiophosphorylation of rMLC showed that the increase in force produced by chronic AlF exposure required Ca(2+) during activation to be manifest. Unlike the acute response to receptor agonists, which is mediated solely by increases in rMLC phosphorylation, chronic direct activation of G proteins further increases Ca(2+) sensitivity in airways by additional mechanisms that are independent of rMLC phosphorylation.
Yoshimura
H
H
Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Jones
K A
KA
Perkins
W J
WJ
Kai
T
T
Warner
D O
DO
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004285:Dogs; D004351:Drug Resistance; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D017616:Magnesium Compounds / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D017607:Aluminum Compounds; D019332:Endothelin-1; D017616:Magnesium Compounds; D018994:Myosin Light Chains; C434208:magnesium adenosine5'-O-(3-thiophosphate); C050992:tetrafluoroaluminate; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D005459:Fluorides; D002118:Calcium