Limits...
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.


Related in: MedlinePlus

Effects of KATP channel blockers or a channel opener on pituitary adenylate cyclase-activating peptide (PACAP)-mediated inhibition of pacemaker potentials recorded in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Glibenclamide (an ATP-sensitive K+ channel blocker; 10 µM) blocked PACAP-induced membrane hyperpolarization and reduced the frequency of pacemaker potentials. (B) Pinacidil (100 nM) reduced the frequency of pacemaker potentials and induced hyperpolarization of the cell membrane in colonic ICC. Glibenclamide (10 µM) blocked the pinacidil-induced action. Vertical solid lines show the amplitude of the pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with KATP channel blockers. 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
getmorefigures.php?uid=PMC4553403&req=5

Figure 5: Effects of KATP channel blockers or a channel opener on pituitary adenylate cyclase-activating peptide (PACAP)-mediated inhibition of pacemaker potentials recorded in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Glibenclamide (an ATP-sensitive K+ channel blocker; 10 µM) blocked PACAP-induced membrane hyperpolarization and reduced the frequency of pacemaker potentials. (B) Pinacidil (100 nM) reduced the frequency of pacemaker potentials and induced hyperpolarization of the cell membrane in colonic ICC. Glibenclamide (10 µM) blocked the pinacidil-induced action. Vertical solid lines show the amplitude of the pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with KATP channel blockers. Bars represent the means±SE. *Asterisks indicate a statistically significantly difference from controls (p<0.05). Con, control.

Mentions: To investigate the role of ATP-sensitive K+ (KATP) channels in PACAP action on colonic ICC, we tested the effects of PACAP when combined with glibenclamide (KATP channel blocker). First, we checked the PACAP (1 nM)-induced inhibitory action on pacemaker potentials in colonic ICC, and then co-treated with glibenclamide (10 µM). Glibenclamide inhibited the effects of PACAP, and ICC returned to normal pacemaker potential conditions (Fig. 5A). To confirm this result, we tested the effects of pinacidil, a KATP channel opener. Pinacidil (100 nM) had an inhibitory action on pacemaker potentials in colonic ICC, similar to PACAP. This effect was rescued by co-treatment with glibenclamide (Fig. 5B). Fig. 5C and D show that no significant difference was observed between PACAP alone and PACAP with glibenclamide (n=3~4).


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 KATP channel blockers or a channel opener on pituitary adenylate cyclase-activating peptide (PACAP)-mediated inhibition of pacemaker potentials recorded in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Glibenclamide (an ATP-sensitive K+ channel blocker; 10 µM) blocked PACAP-induced membrane hyperpolarization and reduced the frequency of pacemaker potentials. (B) Pinacidil (100 nM) reduced the frequency of pacemaker potentials and induced hyperpolarization of the cell membrane in colonic ICC. Glibenclamide (10 µM) blocked the pinacidil-induced action. Vertical solid lines show the amplitude of the pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with KATP channel blockers. 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 5: Effects of KATP channel blockers or a channel opener on pituitary adenylate cyclase-activating peptide (PACAP)-mediated inhibition of pacemaker potentials recorded in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Glibenclamide (an ATP-sensitive K+ channel blocker; 10 µM) blocked PACAP-induced membrane hyperpolarization and reduced the frequency of pacemaker potentials. (B) Pinacidil (100 nM) reduced the frequency of pacemaker potentials and induced hyperpolarization of the cell membrane in colonic ICC. Glibenclamide (10 µM) blocked the pinacidil-induced action. Vertical solid lines show the amplitude of the pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with KATP channel blockers. Bars represent the means±SE. *Asterisks indicate a statistically significantly difference from controls (p<0.05). Con, control.
Mentions: To investigate the role of ATP-sensitive K+ (KATP) channels in PACAP action on colonic ICC, we tested the effects of PACAP when combined with glibenclamide (KATP channel blocker). First, we checked the PACAP (1 nM)-induced inhibitory action on pacemaker potentials in colonic ICC, and then co-treated with glibenclamide (10 µM). Glibenclamide inhibited the effects of PACAP, and ICC returned to normal pacemaker potential conditions (Fig. 5A). To confirm this result, we tested the effects of pinacidil, a KATP channel opener. Pinacidil (100 nM) had an inhibitory action on pacemaker potentials in colonic ICC, similar to PACAP. This effect was rescued by co-treatment with glibenclamide (Fig. 5B). Fig. 5C and D show that no significant difference was observed between PACAP alone and PACAP with glibenclamide (n=3~4).

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.


Related in: MedlinePlus