Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In this study, the authors explored the utility of a descriptive and predictive bionetwork model for
phospholipase C
-coupled calcium signalling pathways, built with non-kinetic experimental information. Boolean models generated from these data yield oscillatory activity patterns for both the endoplasmic reticulum resident inositol-1,4,5-trisphosphate receptor (IP(3)R) and the plasma-membrane resident canonical
transient receptor potential channel 3
(
TRPC3
). These results are specific as randomisation of the Boolean operators ablates oscillatory pattern formation. Furthermore, knock-out simulations of the IP(3)R,
TRPC3
and multiple other proteins recapitulate experimentally derived results. The potential of this approach can be observed by its ability to predict previously undescribed cellular phenotypes using in vitro experimental data. Indeed, our cellular analysis of the developmental and calcium-regulatory protein, DANGER1a, confirms the counter-intuitive predictions from our Boolean models in two highly relevant cellular models. Based on these results, the authors theorise that with sufficient legacy knowledge and/or computational biology predictions, Boolean networks can provide a robust method for predictive modelling of any biological system. [Includes supplementary material].
...
PMID:Exploring phospholipase C-coupled Ca(2+) signalling networks using Boolean modelling. 2163 91
Adenosine, a regulator of cardiovascular development and renal function, constricts renal afferent arterioles by inducing intracellular Ca
2+
concentration ([Ca
2+
]
i
) elevation in smooth muscle cells (SMCs) via activation of its cognate A
1
receptors (A
1
Rs). Mechanisms that underlie A
1
R-dependent [Ca
2+
]
i
elevation in renal vascular SMCs are not fully resolved. Whether A
1
R expression and function in preglomerular microvessels are dependent on postnatal kidney maturation is also unclear. In this study, we show that selective activation of A
1
Rs by 2-chloro-
N
6
-cyclopentyladenosine (CCPA) does not stimulate store-operated Ca
2+
entry in afferent arterioles isolated from neonatal pigs. However, CCPA-induced [Ca
2+
]
i
elevation is dependent on
phospholipase C
and
transient receptor potential cation channel, subfamily C, member 3
(
TRPC3
). Basal [Ca
2+
]
i
was unchanged in afferent arterioles isolated from newborn (0-day-old) pigs compared with their 20-day-old counterparts. By contrast, CCPA treatment resulted in significantly larger [Ca
2+
]
i
in afferent arterioles from 20-day-old pigs. A
1
R protein expression levels in the kidneys and afferent arterioles were unaltered in 0- vs. 20-day-old pigs. However, the
TRPC3
channel protein expression level was ~92 and 78% higher in 20-day-old pig kidneys and afferent arterioles, respectively. These data suggest that activation of A
1
Rs elicits receptor-operated Ca
2+
entry in porcine afferent arterioles, the level of which is dependent on postnatal maturation of
TRPC3
channels. We propose that
TRPC3
channels may contribute to the physiology and pathophysiology of A
1
Rs.
...
PMID:Adenosine A
1
receptor-operated calcium entry in renal afferent arterioles is dependent on postnatal maturation of TRPC3 channels. 2885 89
