Effects of cannabinoids on adrenaline release from adrenal medullary cells

The objective of the present study was to analyse the peripheral effects of cannabinoids on adrenaline release from adrenal chromaffin cells.

In pithed rabbits with electrically stimulated sympathetic outflow, intravenous injection of the cannabinoid receptor agonists WIN55212-2 and CP55940 (5, 50 and 500 μg kg⁻¹) markedly lowered the plasma adrenaline concentration. The effect of WIN55212-2 was attenuated by the selective CB₁ cannabinoid receptor antagonist SR141716A (500 μg kg⁻¹). WIN55212-3 (same doses as WIN55212-2), the enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect on the plasma adrenaline concentration.

In rabbit isolated adrenal glands, the release of adrenaline elicited by electrical stimulation was measured by fast cyclic voltammetry. Electrically-evoked adrenaline release was inhibited by WIN55212-2 (0.3, 1, 3 and 10 μm) and this effect was antagonized by SR141716A (1 μm). The non-cholinergic component of adrenaline release observed after blockade of nicotinic (by hexamethonium 100 μm) and muscarinic (by atropine 0.5 μm) acetylcholine receptors was not depressed by WIN55212-2. WIN55212-3 (10 μm) had no effect on adrenaline release.

No detectable specific CB₁ receptor binding and mRNA expression were found in rabbit adrenal glands with autoradiography and in situ hybridization.

The results show that cannabinoids inhibit adrenaline secretion in rabbit isolated adrenal glands; the likely mechanism is a presynaptic CB₁ receptor-mediated inhibition of acetylcholine release from preganglionic sympathetic neurons. The inhibition of adrenaline secretion in adrenal glands most probably accounts for the decrease in the plasma adrenaline concentration observed after cannabinoid administration in pithed rabbits.