Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported previously that a large-conductance Ca2+-activated K+ (BK(Ca)) channel constitutes a significant fraction of the K+ current in human dermal fibroblasts, and that nitric oxide (NO) increases the open-channel probability (NPo) of BK(Ca) channels via a soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway. The purpose of this study was to investigate whether the adenylate cyclase (AC)/cAMP/protein kinase A (PKA) pathway may also be involved in NO action on BK(Ca) channels in human dermal fibroblasts. Electrophysiological single-channel recordings were performed on fifth-passage cells of human penile skin cultures. KT5720 (specific PKA inhibitor) blocked the stimulatory effect of sodium nitroprusside (NO donor) on BK(Ca) channels. By contrast, forskolin (AC activator) or 8-bromo-cAMP (cell-permeable cAMP analog) did not increase the NPo of the channel. The PKA catalytic subunit (PKAcs) alone did not increase the NPo of the channel in cell-attached and inside-out patches, however, PKAcs with cGMP increased the NPo. In contrast, PKAcs with cGMP did not increase the NPo of BK(Ca) channels with 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one pretreatment, and KT5720 pretreatment also blocked the stimulatory effect of 8-Br-cGMP. In conclusion, the present data suggest the involvement of PKA in the stimulatory effect of NO on the BK(Ca) channel in human dermal fibroblasts through cGMP.
J Invest Dermatol 2007 Nov
PMID:Involvement of protein kinase A in nitric oxide stimulating effect on a BK(Ca) channel of human dermal fibroblasts. 1755 66

The proinflammatory cytokine IL-6 is released in the skin following UVB irradiation, but its potential for photoimmune modulation remains unclear. This study utilizes IL-6-deficient mice to demonstrate that IL-6 does not contribute to the normal contact hypersensitivity response, nor to its systemic suppression by UVB radiation or cis-urocanic acid. In contrast, IL-6 was required for the attenuation of UVB- or cis-urocanic acid-induced immunosuppression by sequential or concomitant UVA irradiation. The IL-6 was essential for several reactions previously established to be relevant for UVA photoimmune protection, namely the induction of heme oxygenase-1 (HO-1), the activity of its product carbon monoxide in activating guanylyl cyclase, and the consequent elevation of cutaneous cyclic guanosine monophosphate concentration. In addition, IL-6-deficient mouse skin had an elevated constitutive overexpression of HO activity, apparently not associated with photoimmune protection. This suggested that both the cutaneous level of HO activity, and the receptiveness of the HO-1 gene to stressors like UVA, normally controlled by promoter-binding repressor proteins, may also be under IL-6 control. Thus IL-6 has an important photoimmune protective function through interaction at several levels in the pathway determining the immunologically advantageous actions of UVA radiation. This may constitute a valuable endogenous antiphotocarcinogenic regulatory mechanism.
J Invest Dermatol 2009 Jun
PMID:The role of interleukin-6 in UVA protection against UVB-induced immunosuppression. 1911 May 42


<< Previous 1 2