RhoA kinase and protein kinase C participate in regulation of rabbit stomach fundus smooth muscle contraction. Br J Pharmacol 2002 Dec;137(7):983-92
Date
11/14/2002Pubmed ID
12429570Pubmed Central ID
PMC1573575DOI
10.1038/sj.bjp.0704952Scopus ID
2-s2.0-0036898808 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
1. The degree to which the RhoA kinase (ROK) blockers, Y-27632 (1 micro M) and HA-1077 (10 micro M), and the PKC blocker, GF-109203X (1 micro M), reduced force produced by carbachol, a muscarinic receptor agonist, and phenylephrine, an alpha-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 ( approximately 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.
Author List
Ratz PH, Meehl JT, Eddinger TJAuthor
Thomas Eddinger PhD Bioological Sciences in the Biology department at Marquette UniversityMESH terms used to index this publication - Major topics in bold
1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAdrenergic alpha-Agonists
Amides
Animals
Carbachol
Dose-Response Relationship, Drug
Enzyme Inhibitors
Female
Gastric Fundus
In Vitro Techniques
Indoles
Intracellular Signaling Peptides and Proteins
Maleimides
Muscle Contraction
Muscle Relaxants, Central
Muscle, Smooth
Phenylephrine
Protein Kinase C
Pyridines
Rabbits
Stomach
Urinary Bladder
rho-Associated Kinases
