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Extraadrenal adrenaline formation by two separate enzymes.
M G Ziegler1, B Kennedy, H Elayan
1Department of Medicine, University of California, San Diego Medical Center 92103.
Experientia
|August 15, 1989
Summary
This study reveals that tissues beyond the adrenal medulla can synthesize adrenaline (A) using the enzyme phenylethanolamine-N-methyltransferase (PNMT). These non-neuronal enzymes contribute significantly to tissue and urine adrenaline levels.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- Adrenaline (epinephrine) is primarily synthesized in the adrenal medullae via phenylethanolamine-N-methyltransferase (PNMT).
- The contribution of extra-adrenal tissues to circulating adrenaline levels remains incompletely understood.
Purpose of the Study:
- To investigate the capacity of various tissues to synthesize adrenaline.
- To identify the enzymes and mechanisms involved in extra-adrenal adrenaline formation.
Main Methods:
- Surgical removal of adrenal medullae tissue in a model system.
- Quantification of adrenaline levels in different tissues post-adrenalectomy.
- Development and application of a novel assay to measure de novo tissue adrenaline formation.
- Enzymatic assays to identify PNMT and other N-methylating enzymes in extra-adrenal tissues.
Main Results:
- Adrenaline levels in various tissues post-adrenalectomy ranged from 22% (heart) to 125% (liver) of control levels.
- A novel assay confirmed that numerous tissues possess the capability to synthesize adrenaline.
- The enzyme phenylethanolamine-N-methyltransferase (PNMT) was identified in these tissues, alongside another enzyme capable of N-methylating noradrenaline and dopamine.
- These identified enzymes are non-neuronal and inducible.
Conclusions:
- Extra-adrenal tissues synthesize a significant fraction of tissue and urine adrenaline.
- Non-neuronal, inducible enzymes, including PNMT, play a crucial role in adrenaline synthesis outside the adrenal medulla.