[PDF][PDF] Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage

O Thastrup, AP Dawson, O Scharff, B Foder… - Agents and …, 1989 - academia.edu
O Thastrup, AP Dawson, O Scharff, B Foder, PJ Cullen, BK Drøbak, PJ Bjerrum…
Agents and actions, 1989academia.edu
Hormones, neurotransmitters, growth factors, and other extracellular stimuli communicate
with their target cells through a specific stimulation of surface receptors that further transduce
the information to a limited number of intracellular second messenger molecules. Among
these recognized messengers are inositol 1, 4, 5-trisphosphate (Ins-1, 4, 5-Pa) and
diacylglycerol (DG) which constitute an interacting pair of signals that induce discharge of
intracellular sequestered Ca 2+[1] and activation of membrane bound protein kinase C [2] …
Hormones, neurotransmitters, growth factors, and other extracellular stimuli communicate with their target cells through a specific stimulation of surface receptors that further transduce the information to a limited number of intracellular second messenger molecules. Among these recognized messengers are inositol 1, 4, 5-trisphosphate (Ins-1, 4, 5-Pa) and diacylglycerol (DG) which constitute an interacting pair of signals that induce discharge of intracellular sequestered Ca 2+[1] and activation of membrane bound protein kinase C [2], respectively. The main features of this bidirectional signalling pathway have been described in several recent reviews [eg 3, 4]. We will focus on the relationship between inositol phosphates and intracellular Ca 2+ regulation as examined by use of the sesquiterpene lactone, thapsigargin. Thapsigargin has proven a valuable new pharmacological probe that interacts with a discrete step in Ca z+ homeostasis events.
The inositol phosphates comprise a very complex group of naturally occurring compounds. In theory, 66 different substances can be obtained on phosphorylation of myo-inositol [5], and over 20 different inositol phosphates have now been detected in mammalian cells. However, only Ins-l, 4, 5-P 3 has been assigned an undisputed physiological role.
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