Non-cholinergic component of rat splanchnic nerves predominates at low neuronal activity and is eliminated by naloxone.

1. Effects of nicotinic (mecamylamine) and muscarinic (atropine) receptor antagonists were investigated on the secretion of catecholamines evoked by stimulation of splanchnic nerve terminals and acetylcholine in the isolated perfused adrenal gland of the rat to determine whether non-cholinergic substances released from nerve terminals participate in the secretion of catecholamines. 2. Increasing the frequency of stimulation from 0.5 to 10 Hz (300 pulses) caused enhanced secretion of catecholamines (26-110 ng/collection period). After blockade of nicotinic and muscarinic receptors with mecamylamine and atropine, the secretion was reduced by 40, 65 and 80% at 0.5, 1 and 10 Hz, respectively. Acetylcholine-evoked secretion of catecholamines, which was roughly equivalent to that produced by stimulation at 10 Hz, was blocked by over 90% by the cholinergic antagonists. 3. Naloxone (3-300 microM) caused a concentration-dependent inhibition of catecholamine secretion evoked by stimulation of splanchnic nerves (1 Hz); acetylcholine-evoked secretion was much less affected by naloxone. 4. The secretion of catecholamines that remained after blockade of cholinergic receptors at different frequencies of stimulation (see 2 above) was almost completely inhibited by inclusion of 30 microM-naloxone in the medium. The inhibitory effect of naloxone was concentration dependent (3-30 microM) and reversible. 5. Splanchnic nerve-evoked secretion of catecholamines was facilitated by 400% in the presence of tetraethylammonium or tetraethylammonium plus mecamylamine and atropine. The facilitatory effect of tetraethylammonium was inversely related to the frequency of stimulation. 6. The residual secretion of catecholamines obtained after blockade of cholinergic receptors was facilitated by increasing concentrations of tetraethylammonium (1-5 mM). 30 microM-naloxone antagonized the facilitatory effects of tetraethylammonium at 1 and 3 mM by 60% and 25%, respectively, but failed at 5 mM-tetraethylammonium; higher concentrations of naloxone (100 microM) were also ineffective. 7. It is concluded that neurally evoked secretion of catecholamines is mediated by acetylcholine and a non-cholinergic substance(s); the contribution of non-cholinergic substance(s) predominates at low neuronal activity, whereas that of acetylcholine is maximum at high neuronal activity. Blockade of the non-cholinergic component by naloxone suggests that an opioid peptide may be involved in the secretion of catecholamines in the rat adrenal medulla.