Protein kinase regulation of muscarinic receptor signalling in colonic smooth muscle

Content Provider	Scilit
Author	Zhang, Lubo Buxton, Iain L. O.
Copyright Year	1993
Description	Journal: British Journal of Pharmacology 1 We have previously demonstrated that $M_{2}$ and $M_{3}$ muscarinic receptors coexist in the circular smooth muscle of canine promixal colon. Activation of receptors of the $M_{2}$ subtype leads to inhibition of adenylyl cyclase activity through the GTP-binding protein, $G_{i}$, while $M_{3}$ receptors are coupled to a pertussis toxin-insensitive GTP-binding protein and mediate phosphoinositide hydrolysis. 2 In the present study, the interactions between these second messenger systems were examined. Activation of either protein kinase C or adenosine 3′:5′-cyclic monophosphate (cyclic AMP)-dependent protein kinase attenuated carbachol-stimulated phosphoinositide hydrolysis without affecting basal activity. Activation of both protein kinases produced greater attenuation of inositol 1,4,5-trisphosphate formation than activation of either kinase alone. 3 In contrast to its inhibitory effect on phosphoinositide hydrolysis, activation of protein kinase C had no effect on adenylyl cyclase activity. 4 Activation of protein kinase C by phorbol ester treatment resulted in the sequestration of $M_{3}$ muscarinic receptors from the cell surface without effecting the $M_{2}$ muscarinic receptor population. Sequestered $M_{3}$ muscarinic receptors were not rapidly degraded. 5 In contrast, elevation of cellular cyclic AMP decreased the affinity of cell surface muscarinic receptors for an antagonist radioligland without affecting their density. 6 Muscarinic agonist binding was not affected by either activation of protein kinase C or elevation of cellular cyclic AMP. 7 These data support the notion of negative feedback by protein kinase C and cyclic AMP-dependent protein kinase on phosphoinositide hydrolysis. In canine colonic circular smooth muscle this negative feedback regulation of inositol phosphate generation by muscarinic receptor stimulation does not appear to involve the guanine nucleotide binding protein:receptor interaction.
Related Links	http://europepmc.org/articles/pmc1908018?pdf=render https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1993.tb12850.x
Ending Page	621
Page Count	9
Starting Page	613
e-ISSN	14765381
DOI	10.1111/j.1476-5381.1993.tb12850.x
Journal	British Journal of Pharmacology
Issue Number	3
Volume Number	108
Language	English
Publisher	Wiley-Blackwell
Publisher Date	1993-03-01
Access Restriction	Open
Subject Keyword	Journal: British Journal of Pharmacology Muscarinic Receptors Protein Kinase C Cyclic Amp-dependent Protein Kinase Phosphoinositide Hydrolysis Smooth Muscle
Content Type	Text
Resource Type	Article