Catecholamine secretion in trout chromaffin cells experiencing nicotinic receptor desensitization is maintained by non-cholinergic neurotransmission.

The goal of the present study was to assess the catecholamine secretory capabilities of rainbow trout Oncorhynchus mykiss chromaffin cells experiencing desensitization of the nicotinic receptor. It was hypothesized that the potential to secrete catecholamines could be maintained under conditions of nicotinic receptor desensitization owing to activation of non-cholinergic release pathways. An in situ model for chromaffin cell nicotinic receptor desensitization was developed by perfusing a posterior cardinal vein preparation with saline containing 10[sup -5] mol l[sup -1] nicotine. Under such conditions of desensitization, the chromaffin cells were largely unresponsive to high-frequency (20 Hz) electrical stimulation; the minimal remaining secretory response was abolished by addition of the nicotinic receptor antagonist hexamethonium (10[sup -3] mol l[sup -1]). In marked contrast, however, the capacity to secrete catecholamines in response to low-frequency (1 Hz) electrical stimulation was unaffected by nicotinic receptor desensitization or by cholinergic receptor blockade (hexamethonium plus atropine). In preparations experiencing nicotinic receptor desensitization, the stimulatory effect of low-frequency (1 Hz) stimulation on catecholamine secretion was reduced by 43% in the presence of the VPAC receptor antagonist, VIP[sub 6-28]. The stimulatory effect of high-frequency (20 Hz) stimulation was unaffected by VIP[sub 6-28]. Catecholamine secretion evoked by cod VIP (10[sup -11] mol kg[sup -1]) and homologous angiotensin II ([Asn¹, Val[sup 5]] Ang II; 5×10[sup -7] mol kg[sup -1]) was markedly enhanced (107 and 97%, respectively) in desensitized preparations. However, the secretory response to the muscarinic receptor agonist methylcholine (1×10[sup -3] mol kg[sup -1]) was unchanged by desensitization. The results of this study demonstrate that exploitation of non-cholinergic mechanisms, including peptidergic pathways activated during low-frequency neuronal stimulation, is a potential strategy whereby catecholamine secretion from trout chromaffin cells can be maintained during periods of nicotinic receptor desensitization. [ABSTRACT FROM AUTHOR]