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.


Effects of NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) on pituitary adenylate cyclase-activating peptide (PACAP)-induced responses of pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) L-NAME (a competitive inhibitor of NO synthase; 10 µM) did not have any effect on PACAP-induced action in colonic ICC. (B) ODQ (an inhibitor of guanylate cyclase; 10 µM) also did not show any effect on PACAP-induced action in colonic ICC. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with L-NAME or ODQ. Bars represent the means±SE. Con, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4553403&req=5

Figure 7: Effects of NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) on pituitary adenylate cyclase-activating peptide (PACAP)-induced responses of pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) L-NAME (a competitive inhibitor of NO synthase; 10 µM) did not have any effect on PACAP-induced action in colonic ICC. (B) ODQ (an inhibitor of guanylate cyclase; 10 µM) also did not show any effect on PACAP-induced action in colonic ICC. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with L-NAME or ODQ. Bars represent the means±SE. Con, control.

Mentions: To study whether PACAP-induced action on colonic ICC is regulated by nitric oxide (NO) signal pathways, L-NAME (a competitive inhibitor of NO synthase) or ODQ (an inhibitor of guanylate cyclase) were tested in combination with PACAP. Pretreatment with L-NAME (10 µM) or ODQ (10 µM) did not affect PACAP-induced inhibitory action or hyperpolarization of the membrane in colonic ICC (Fig. 7A and B). Fig. 7C and D show that no significant differences in frequency or resting membrane potentials were observed between PACAP alone and PACAP with L-NAME or ODQ (n=4~5).


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 NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) on pituitary adenylate cyclase-activating peptide (PACAP)-induced responses of pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) L-NAME (a competitive inhibitor of NO synthase; 10 µM) did not have any effect on PACAP-induced action in colonic ICC. (B) ODQ (an inhibitor of guanylate cyclase; 10 µM) also did not show any effect on PACAP-induced action in colonic ICC. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with L-NAME or ODQ. Bars represent the means±SE. Con, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Effects of NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) on pituitary adenylate cyclase-activating peptide (PACAP)-induced responses of pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) L-NAME (a competitive inhibitor of NO synthase; 10 µM) did not have any effect on PACAP-induced action in colonic ICC. (B) ODQ (an inhibitor of guanylate cyclase; 10 µM) also did not show any effect on PACAP-induced action in colonic ICC. (C) and (D) summarize the effects of PACAP on pacemaker potentials in colonic ICC with L-NAME or ODQ. Bars represent the means±SE. Con, control.
Mentions: To study whether PACAP-induced action on colonic ICC is regulated by nitric oxide (NO) signal pathways, L-NAME (a competitive inhibitor of NO synthase) or ODQ (an inhibitor of guanylate cyclase) were tested in combination with PACAP. Pretreatment with L-NAME (10 µM) or ODQ (10 µM) did not affect PACAP-induced inhibitory action or hyperpolarization of the membrane in colonic ICC (Fig. 7A and B). Fig. 7C and D show that no significant differences in frequency or resting membrane potentials were observed between PACAP alone and PACAP with L-NAME or ODQ (n=4~5).

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.