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

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-alpha]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.

Control Mechanisms of Ovarian Follicle Development by Follicle Stimulating Hormone and Pituitary Adenylate Cyclase-activating Polypeptide / 대한불임학회지

OBJECTIVE: Pituitary adenylate cyclase-activating polypeptide (PACAP), a novel hypothalamic neuropeptide, has been suggested to play a role in ovarian folliculogenesis. The present study evaluated the effect of PACAP on the growth of preantral follicles. METHODS: Preantral follicles were mechanically isolated from ovaries of 21-day-old rats and cultured in groups for 3 days in serum-free medium in the absence or presence of PACAP-38 (10-6 M). RESULTS: Treatment with PACAP-38 resulted in an increase in follicle diameter by 75% whereas treatment with follicle stimulating hormone (FSH) increased follicle diameter by 65%. PACAP-38 treatment enhanced the granulosa cell proliferation as measured by thymidine incorporation analysis. Furthermore, the production of progesterone by cultured granulosa cells and GFSHR-17 cell line was stimulated by PACAP-38. Interestingly, PACAP enhanced FSH action on stimulation of SF-1 and aromatase gene expression. CONCLUSION: The present results demonstrate that PACAP stimulated preantral follicle growth by potentiating proliferation and by stimulating steroidogenesis.

Control Mechanisms of Ovulation by Pituitary Adenylate Cyclase-Activating Polypeptide / 대한불임학회지

No abstract available.

Role of Pituitary Adenylate Cyclase Activating Polypeptide-(1-27) in the Clitorial Cavernosum Smooth Muscle / 대한비뇨기과학회지

PURPOSE: Pituitary adenylate cyclase-activating polypeptide (PACAP) showed the relaxant effect and distribution patterns in the penile corpus cavernosum. We investigated the presence, distribution, and effects of PACAP-(1-27) in the clitoral cavernosum (CC). MATERIALS AND METHODS: The isometric tension was measured in the strip of rabbit CC. Immunohistochemistry was used to localize PACAP-(1-27) immunoreactivity in nerve fibers in CC. Possible co-localization of the PACAP-(1-27) immunoreactive nerve fiber with other nerve fiber was investigated by application of double immunofluorescent labeling technique using antibody to protein gene product 9.5 (PGP 9.5). Western blotting was used to identify the expression of PACAP-(1-27) protein. RESULTS: The pre-contracted CC smooth muscle strip with phenylephrine was relaxed dose-dependently with PACAP-(1-27). PACAP-(6-27), PACAP-(1-27) receptor antagonist did not affect the PACAP-(1-27) induced relaxant responses. Pre-treatment with Nw- nitro-L-arginine methyl ester (NO synthase inhibitor) did not affect the relaxation induced by PACAP-(1-27). CC was not stained by anti-human PACAP-(1-27) guinea pig polyclonal antibody and the immunoreactivity for anti-human PGP 9.5 mouse monoclonal antibody was observed throught the CC. Western blotting demonstrated the presence of immunoreactive protein band corresponding to 35 KDa PACAP-(1-27). CONCLUSIONS: The present study shows that PACAP-(1-27) has a possible role in the modulation of smooth muscle tone of the CC resulting in erection.