Stimulatory actions of caffeic acid phenethyl ester, a known inhibitor of NF-kappaB activation, on Ca2+-activated K+ current in pituitary GH3 cells.
Caffeic acid phenethyl ester (CAPE), a phenolic antioxidant derived from the propolis of honeybee hives, is known to be an inhibitor of activation of nuclear transcript factor NF-kappaB. Its effects on ion currents have been investigated in pituitary GH(3) cells. This compound increased Ca(2+)-activated K(+) current (I(K(Ca))) in a concentration-dependent manner with an EC(50) value of 14 +/- 2 microm. However, the magnitude of CAPE-induced stimulation of I(K(Ca)) was attenuated in GH(3) cells preincubated with 2,2'-azo-bis-(2-amidinopropane) hydrochloride (100 microm) or t-butyl hydroperoxide (1 mm). CAPE (50 microm) slightly suppressed voltage-dependent L-type Ca(2+) current. In inside-out configuration, CAPE (20 microm) applied to the intracellular face of the detached patch enhanced the activity of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels with no modification in single-channel conductance. After BK(Ca) channel activity was increased by CAPE (20 microm), subsequent application of nordihydroguaiaretic acid (20 microm) did not further increase the channel activity. CAPE-stimulated channel activity was dependent on membrane potential. CAPE could also increase Ca(2+) sensitivity of BK(Ca) channels in these cells. Its increase in the open probability could primarily involve a decrease in the mean closed time. In current-clamp conditions, CAPE hyperpolarized the membrane potential and reduced the firing of action potentials. The stimulatory effects on these channels may partly contribute to the underlying mechanisms through which this compound influences the functional activities of neurons or neuroendocrine cells. Caution has to be used in attributing its response in the activation of NF-kappaB.
Lin
Ming-Wei
MW
Institute of Basic Medical Sciences, National Cheng-Kung University Medical College, Tainan 701, Taiwan.
Yang
Su-Rong
SR
Huang
Mei-Han
MH
Wu
Sheng-Nan
SN
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009637:Masoprocol / Q000737:chemistry / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018408:Patch-Clamp Techniques / Q000379:methods; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists* / Q000502:physiology; D051381:Rats; D019782:Riluzole / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000578:Amidines; D002109:Caffeic Acids; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D016328:NF-kappa B; D024681:Potassium Channels, Calcium-Activated; C046728:2,2'-azobis(2-amidinopropane); D009637:Masoprocol; D019782:Riluzole; D020122:tert-Butylhydroperoxide; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D002118:Calcium