G. Loirand et al., ARF-INDEPENDENT INHIBITION OF THE CARBACHOL-INDUCED CONTRACTIONS BY BREFELDIN-A IN INTESTINAL SMOOTH-MUSCLE, American journal of physiology. Cell physiology, 42(3), 1997, pp. 816-821
The aim of this study was to determine whether an ADP ribosylation fac
tor (ARF)-regulated pathway is involved in the carbachol-induced contr
action in rat intestinal smooth muscle. Brefeldin A, a known inhibitor
of the guanine nucleotide exchange activity on ARF, reversibly inhibi
ted the carbachol-induced contraction in intact ileal muscle strips, w
hereas the carbachol-and guanosine 5'-O-(3-thiotriphosphate)-induced i
ncreases in the Ca2+ sensitivity of myofilaments in beta-escin-permeab
ilized strips were not affected. The high-K+-induced contraction in in
tact strips was also inhibited by brefeldin A. In isolated ileal myocy
tes, brefeldin A inhibited the Ca2+ channel current, indicating that t
he inhibitory effect of brefeldin A in intact cells is related to an i
nhibition of voltage-dependent Ca2+ channels. Furthermore, the loading
of permeabilized strips with the combination of the recombinant fully
myristoylated ARF1, the guanine nucleotide exchange factor ARNO, and
guanosine 5'-triphosphate did not change the tone at constant pCa (6.4
5) and did not modify the carbachol- and guanosine 5'-O-(3-thiotriphos
phate)-induced Ca2+ sensitization. Taken together, these findings sugg
est that an ARF-dependent pathway is not involved in the carbachol-ind
uced contraction.