Receptor-coupled, permeabilized smooth muscle. Role of the phosphatidylinositol cascade, G-proteins, and modulation of the contractile response to Ca2+.
alpha-Adrenergic (phenylephrine) and muscarinic (carbachol) agonists and inositol 1,4,5-trisphosphate caused calcium release and contractions in smooth muscle strips permeabilized with Staphylococcus aureus alpha-toxin. The responses to phenylephrine and carbachol required or were potentiated by added GTP and could be inhibited by GDP beta S. GTP and phenylephrine also increased the contractile response of permeabilized portal vein smooth muscle to cytoplasmic Ca2+. We conclude that while the G-protein-coupled phosphatidylinositol cascade, through inositol 1,4,5-trisphosphate-induced calcium release, is a major mechanism of pharmacomechanical coupling, a second G-protein-mediated pathway that modulates the calcium sensitivity of the regulatory contractile proteins also exists.
Kitazawa
T
T
Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6083.
Kobayashi
S
S
Horiuti
K
K
Somlyo
A V
AV
Somlyo
A P
AP
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006168:Guinea Pigs; D006460:Hemolysin Proteins; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000502:physiology*; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013211:Staphylococcus aureus
D001427:Bacterial Toxins; D006150:Guanine Nucleotides; D006460:Hemolysin Proteins; D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; C021091:staphylococcal alpha-toxin; D010656:Phenylephrine; D002217:Carbachol; D019204:GTP-Binding Proteins; D002118:Calcium