APPS November 2002 Meeting Abstract 1328

In chromaffin cells of the adrenal medulla, we have shown previously¹ that hypoxia, by closure of SK channels, can trigger depolarisation and the secretion of catecholamines. This non-neurogenic hypoxia-evoked secretion of catecholamines is suppressed after the development of adrenal innervation. Of the neurotransmitters that have been identified in the splanchnic nerves, we proposed that opioid peptides have actions that are most likely to account for the suppression the non-neurogenic catecholamine response to hypoxia. The effects of the specific opioid agonists DPDPE (δ-agonist), U-62066 (κ-agonist) and DALDA (µ-agonist) on the hypoxia-evoked response were investigated both in whole gland preparations and isolated adrenal chromaffin cells using amperometry, whole-cell patch clamping and measurement of cytosolic [Ca²⁺]. The combined application of µ- and κ-type agonists inhibited the hypoxia-evoked catecholamine secretion from whole perfused adrenal gland. Whole cell patch clamp revealed that both µ- and κ-agonists decreased the voltage-dependent Ca²⁺ current, and that the µ, but not the κ, agonist increased the membrane conductance by an action on SK-type K⁺ channels. The opioid-evoked increase in SK current appears to offset the hypoxic suppression of this current, and this, along with the reduction in voltage-dependent Ca²⁺ current , accounts for the ability of opioid agonists to inhibit the hypoxia-evoked secretion of catecholamines. The data are compatible with the proposal that opioids may be responsible for the nerve-induced suppression of the hypoxic response of adrenal chromaffin cells.