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Role of Mg-ATP in Norepinephrine Biosynthesis in Intact Chromaffin Granules (1994)

Dhariwal, Kuldeep R. ; Shirvan, Mitchell H. ; Levine, Mark

Oxford, UK : Blackwell Publishing Ltd

Journal of neurochemistry 62 (1994), S. 0

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ISSN: 1471-4159

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: Abstract: Dopamine β-mdriooxygenase converts dopamine to norepinephrine in intact chromaffin granules using intragranular ascorbic acid as a cosubstrate. Mg-ATP with external ascorbic acid is required for maximal norepinephrine biosynthesis. Mechanisms to explain these requirements were investigated specifically using intact granules. The effect of Mg-ATP was independent of membrane potential (ΔΨ) because norepinephrine biosynthesis was unchanged whether ΔΨ was positive or collapsed. Furthermore, the effect of Mg-ATP was independent of absolute intragranular and extragranular pH as well as the pH difference across the chromaffin granule membrane (ΔpH). Nevertheless, norepinephrine biosynthesis was inhibited by N-ethylmaleimide, 4-chloro-7-nitrobenzofurazane, and N, N-dicyclohexylcarbodiimide, specific inhibitors of the secretory vesicle ATPase that may directly affect proton pumping. Biosynthesis occurred normally with other ATPase inhibitors that do not inhibit the ATPase in secretory vesicles. The data indicate that the effect of Mg-ATP with ascorbic acid is mediated by the granule membrane ATPase but independent of maintaining ΔΨ and ApH. An explanation of these findings is that Mg-ATP, via the granule ATPase, may change the rate at which protons or dopamine are made available to dopamine β-monooxygenase.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1471-4159.1994.62010355.x

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