Does acetylcholinesterase inhibition affect catecholamine secretion by adrenomedullary cells?
BACKGROUND
Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells.


OBJECTIVE
To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release.


METHODS
Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48-72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10(-7) to 10(-3) M), for 1-20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether coincubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed in quadruplicate and repeated three times.


RESULTS
Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect. Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+.


CONCLUSIONS
Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells.
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Yehonatan
Y
Sharabi
Reuven
R
Zimlichman
Roshanak
R
Mansouri
Jeffrey
J
Chun
David S
DS
Goldstein
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis*; D002417:Cattle; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004491:Edrophonium / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects
D002395:Catecholamines; D002800:Cholinesterase Inhibitors; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D000804:Angiotensin II; D009538:Nicotine; D004491:Edrophonium; D011188:Potassium