Document Type
Article
Language
eng
Format of Original
10 p.
Publication Date
12-2002
Publisher
Wiley
Source Publication
British Journal of Pharmacology
Source ISSN
0007-1188
Abstract
1. The degree to which the RhoA kinase (ROK) blockers, Y-27632 (1 µM) and HA-1077 (10 µM), and the PKC blocker, GF-109203X (1 µM), reduced force produced by carbachol, a muscarinic receptor agonist, and phenylephrine, an α-adrenoceptor agonist, was examined in rabbit stomach fundus smooth muscle.
2. When examining the effect on cumulative carbachol concentration-response curves (CRCs), ROK and PKC blockers shifted the potency (~EC50) to the right but did not reduce the maximum response.
3. In a single-dose carbachol protocol using moderate (~EC50) and maximum carbachol concentrations, Y-27632 and HA-1077 reduced peak force, but GF-109203X had no effect. By contrast, all three agents inhibited the carbachol contractions of rabbit bladder (detrusor) smooth muscle.
4. Compared to carbachol, phenylephrine produced a weaker maximum response that was not inhibited by phentolamine, atropine nor capsaicin but was inhibited by Y-27632, HA-1077 and GF-109203X.
5. In detrusor, classical down-regulation occurred, but in fundus, up-regulation of responsiveness occurred. This up-regulation in fundus may have been a post-receptor event, because a KCl-induced contraction produced after a carbachol CRC was stronger than one produced before the carbachol stimulus.
6. In conclusion, these data suggest that ROK plays a critical role in the regulation of rabbit fundus smooth muscle contraction, which is distinct from chicken gizzard smooth muscle, where ROK is reported to exist but to not play a role in muscarinic receptor-induced contraction. Additional unique findings are that PKC participates in phenylephrine- but not carbachol-induced contraction in fundus, that carbachol does not activate identical subcellular signalling systems in fundus and detrusor, and that fundus, unlike detrusor, responds to carbachol stimulation with post-receptor up-regulation of contraction.
Recommended Citation
Ratz, Paul H.; Meehl, Joel T.; and Eddinger, Thomas, "RhoA Kinase and Protein Kinase C Participate in Regulation of Rabbit Stomach Fundus Smooth Muscle Contraction" (2002). Biological Sciences Faculty Research and Publications. 6.
https://epublications.marquette.edu/bio_fac/6
Comments
Accepted version. British Journal of Pharmacology, Vol. 137, No. 7 (December 2002): 983-992. DOI. © 2002 Wiley-Blackwell. Used with permission.
The definitive version is available at www3.interscience.wiley.com.