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Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal.

Wu MJ, Kee KH, Na J, Kim SW, Bae Y, Shin DH, Choi S, Jun JY, Jeong HS, Park JS - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K(+) channel blocker).However, neither N (G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity.These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Korea.

ABSTRACT
This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K(+) channel blocker). However, neither N (G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive K(+) channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

No MeSH data available.


Effects of forskolin on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with forskolin (50 nM) had an inhibitory effect on pacemaker potentials, similar to that of pituitary adenylate cyclase-activating peptide (PACAP). (B) Co-treatment with glibenclamde (10 µM) inhibited forsklin-induced action on colonic ICC. (C) and (D) summarize the effects of forskolin on pacemaker potentials in colonic ICC with glibenclamide. Bars represent the means±SE. *Asterisks indicate a statistically significantly difference from controls (p<0.05). Con, control.
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Figure 6: Effects of forskolin on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with forskolin (50 nM) had an inhibitory effect on pacemaker potentials, similar to that of pituitary adenylate cyclase-activating peptide (PACAP). (B) Co-treatment with glibenclamde (10 µM) inhibited forsklin-induced action on colonic ICC. (C) and (D) summarize the effects of forskolin on pacemaker potentials in colonic ICC with glibenclamide. Bars represent the means±SE. *Asterisks indicate a statistically significantly difference from controls (p<0.05). Con, control.

Mentions: To verify the role of cAMP in ICC regulation, we tested the effects of forskolin on pacemaker potentials. Under a current clamp, ICC generated spontaneous pacemaker potentials. The application of 50 nM forskolin induced hyperpolarization of the cell membrane with reduction of frequency (Fig. 6A). Glibenclamide (10 µM) rescued the forskolin-induced hyperpolarization of the ICC membrane and the decreased pacemaker potential frequency (Fig. 6B). Fig. 6C and D show that no significant difference was observed between forskolin alone and forskolin with glibenclamide in ICC (n=10).


Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal.

Wu MJ, Kee KH, Na J, Kim SW, Bae Y, Shin DH, Choi S, Jun JY, Jeong HS, Park JS - Korean J. Physiol. Pharmacol. (2015)

Effects of forskolin on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with forskolin (50 nM) had an inhibitory effect on pacemaker potentials, similar to that of pituitary adenylate cyclase-activating peptide (PACAP). (B) Co-treatment with glibenclamde (10 µM) inhibited forsklin-induced action on colonic ICC. (C) and (D) summarize the effects of forskolin on pacemaker potentials in colonic ICC with glibenclamide. Bars represent the means±SE. *Asterisks indicate a statistically significantly difference from controls (p<0.05). Con, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553403&req=5

Figure 6: Effects of forskolin on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with forskolin (50 nM) had an inhibitory effect on pacemaker potentials, similar to that of pituitary adenylate cyclase-activating peptide (PACAP). (B) Co-treatment with glibenclamde (10 µM) inhibited forsklin-induced action on colonic ICC. (C) and (D) summarize the effects of forskolin on pacemaker potentials in colonic ICC with glibenclamide. Bars represent the means±SE. *Asterisks indicate a statistically significantly difference from controls (p<0.05). Con, control.
Mentions: To verify the role of cAMP in ICC regulation, we tested the effects of forskolin on pacemaker potentials. Under a current clamp, ICC generated spontaneous pacemaker potentials. The application of 50 nM forskolin induced hyperpolarization of the cell membrane with reduction of frequency (Fig. 6A). Glibenclamide (10 µM) rescued the forskolin-induced hyperpolarization of the ICC membrane and the decreased pacemaker potential frequency (Fig. 6B). Fig. 6C and D show that no significant difference was observed between forskolin alone and forskolin with glibenclamide in ICC (n=10).

Bottom Line: The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K(+) channel blocker).However, neither N (G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity.These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Korea.

ABSTRACT
This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K(+) channel blocker). However, neither N (G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive K(+) channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

No MeSH data available.