Tl. Croxton et al., ROLE OF G-PROTEINS IN AGONIST-INDUCED CA2-MUSCLE( SENSITIZATION OF TRACHEAL SMOOTH), American journal of physiology. Lung cellular and molecular physiology, 19(4), 1998, pp. 748-755
Increased sensitivity to intracellular Ca2+ concentration ([Ca2+]) is
an important mechanism for agonist-induced contraction of airway smoot
h muscle, but the signal transduction pathways involved are uncertain.
We studied Ca2+ sensitization with acetylcholine (ACh) and endothelin
(ET)-1 in porcine tracheal smooth muscle by measuring contractions at
a constant [Ca2+] in strips permeabilized with alpha-toxin or beta-es
cin. The peptide inhibitor G protein antagonist 2A (GP Ant-SA), which
has selectivity for G(q) over G(i), inhibited contractile responses to
ET-I,ACh, and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), but
the proportional inhibition of ACh responses was less than that of ET-
1. Pretreatment with pertussis toxin reduced ACh contractions but had
no effect on those of ET-1 or GTP gamma S. Clostridium botulinum C3 ex
oenzyme, which inactivates Rho family monomeric G proteins, caused sim
ilar reductions in contractile responses to ACh, ET-1, and GTP gamma S
. Farnesyltransferase inhibition, which inhibits Ras G proteins, reduc
ed responses to ET-1. We conclude that the heterotrimeric G proteins G
(q) and G(i) both contribute to Ca2+ sensitization by ACh, whereas ET-
1 responses involve G(q) but not G(i). Both G(q) and G(i) pathways lik
ely involve Rho family small G proteins. A Ras-mediated pathway also c
ontributes to Ca2+ sensitization by ET-1 in airway smooth muscle.