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Effect of a peptide inhibitor of protein kinase C on G‐protein‐mediated increase in myofilament Ca 2+ ‐sensitivity in rabbit arterial skinned muscle
Author(s) -
Itoh Takeo,
Suzuki Akito,
Watanabe Yoshimasa
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14061.x
Subject(s) - gtp' , protein kinase c , phosphorylation , guanosine , myosin light chain kinase , chemistry , g protein , muscle contraction , protein phosphorylation , protein kinase a , medicine , contraction (grammar) , endocrinology , biophysics , biochemistry , biology , signal transduction , enzyme
1 To investigate the role of protein kinase C in the increase mediated by guanosine 5′‐triphosphate (GTP)‐binding proteins (G‐proteins) in the sensitivity of the contractile proteins to Ca 2+ in vascular smooth muscle, the effect of a novel peptide inhibitor of protein kinase C (PKC 19–36 ) on Ca 2+ ‐induced contraction and myosin light chain (MLC) phosphorylation was studied in the presence and absence of guanosine 5′‐O‐(3‐thiotriphosphate) (GTP γ S) in β‐escin‐skinned smooth muscle strips of rabbit mesenteric artery. For comparison, the effects were also observed of PKC 19–36 on the action of phorbol 12,13‐dibutylate (PDBu, an activator of PKC) on the two Ca 2+ ‐induced responses. 2 In β‐escin‐skinned strips treated with ionomycin, Ca 2+ (0.1–3 μ m ) concentration‐dependently produced contraction in parallel with an increase in MLC‐phosphorylation. GTP γ S (10 μ m ) and PDBu (0.1 μ m ) each shifted both the Ca 2+ ‐force and Ca 2+ ‐MLC‐phosphorylation relationships to the left without a significant change in either maximum response. The relationship between force and MLC‐phosphorylation was not modified by either GTP γ S or PDBu, indicating that the sensitivity of MLC‐phosphorylation to Ca 2+ is enhanced by both GTP γ S and PDBu. 3 PKC 19–36 itself modified neither the contraction nor MLC‐phosphorylation induced by Ca 2+ but it did block the PDBu‐induced enhancement of these two Ca 2+ ‐induced responses. By contrast, PKC 19–36 did not modify the GTP γ S‐induced enhancement of the two Ca 2+ ‐induced responses. Guanosine 5′‐O‐(2‐thiodiphosphate) (GDP β S) attenuated the GTP γ S‐induced enhancement of the Ca 2+ ‐induced contraction. 4 These results suggest that GTP γ S increases Ca 2+ ‐induced MLC‐phosphorylation through the activation of a PKC‐independent mechanism and thus causes an increase in the sensitivity of the contractile proteins to Ca 2+ in β‐escin‐skinned smooth muscle of rabbit mesenteric artery.