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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 SQ-22536 and cell-permeable 8-bromo-cyclic AMP (8-bromo-cAMP) on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with SQ-22536 (100 µM) showed inhibitory effects on pacemaker potentials. (B) Treatment with 8-bromo-cAMP (100 µM) increased the frequency of pacemaker potentials in colonic ICC. Vertical solid lines show the amplitude of pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials.
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Figure 3: Effects of SQ-22536 and cell-permeable 8-bromo-cyclic AMP (8-bromo-cAMP) on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with SQ-22536 (100 µM) showed inhibitory effects on pacemaker potentials. (B) Treatment with 8-bromo-cAMP (100 µM) increased the frequency of pacemaker potentials in colonic ICC. Vertical solid lines show the amplitude of pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials.

Mentions: To investigate whether PACAP stimulates adenylate cyclase with a subsequent increase in cAMP levels, we tested the effects of SQ-22536 (adenylate cyclase inhibitor) and cell-permeable 8-bromo-cAMP. SQ-22536 (100 µM) inhibited the frequency of pacemaker potentials and induced slight hyperpolarization of the membrane (Fig. 3A). In contrast, 8-bromo-cAMP (100 µM) increased the frequency of pacemaker potentials and slightly depolarized the membrane (Fig. 3B).


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 SQ-22536 and cell-permeable 8-bromo-cyclic AMP (8-bromo-cAMP) on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with SQ-22536 (100 µM) showed inhibitory effects on pacemaker potentials. (B) Treatment with 8-bromo-cAMP (100 µM) increased the frequency of pacemaker potentials in colonic ICC. Vertical solid lines show the amplitude of pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effects of SQ-22536 and cell-permeable 8-bromo-cyclic AMP (8-bromo-cAMP) on pacemaker potentials in cultured interstitial cells of Cajal (ICC) from mouse colon. (A) Treatment with SQ-22536 (100 µM) showed inhibitory effects on pacemaker potentials. (B) Treatment with 8-bromo-cAMP (100 µM) increased the frequency of pacemaker potentials in colonic ICC. Vertical solid lines show the amplitude of pacemaker potentials and horizontal solid lines show the duration of recording (s) of pacemaker potentials.
Mentions: To investigate whether PACAP stimulates adenylate cyclase with a subsequent increase in cAMP levels, we tested the effects of SQ-22536 (adenylate cyclase inhibitor) and cell-permeable 8-bromo-cAMP. SQ-22536 (100 µM) inhibited the frequency of pacemaker potentials and induced slight hyperpolarization of the membrane (Fig. 3A). In contrast, 8-bromo-cAMP (100 µM) increased the frequency of pacemaker potentials and slightly depolarized the membrane (Fig. 3B).

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.