Cytokine interactions with adrenal medullary chromaffin cells.

It is generally accepted that a bi-directional or reciprocal interaction occurs between the immune and neuroendocrine systems, and that this relationship is important for the appropriate physiological functioning of both systems. Similarly, an imbalance in this relationship may contribute to a number of pathologies, most notably those relating to stress. The aim of this article is to consider the interaction of cytokines with the adrenal medulla, a potentially important player in this relationship. The chromaffin cells of the adrenal medulla release catecholamines and a range of biologically active peptides in response to a wide variety of stress-related signals. A growing body of evidence indicates that this stress response is influenced by, and in turn has influence upon, immune signalling. This brief review will focus primarily on the best-described adrenal medullary active cytokines, namely interferon-α, interleukin-6, interleukin-1α/ß and tumour necrosis factor-α. In each case, three key issues will be addressed: the physiologically relevant source of the cytokine; the intracellular signalling events arising from activation of its receptor and finally the cellular consequences of such activation in terms of modulation of gene expression and the secretory output of the chromaffin cells.

Characterization of catecholamine release from deer adrenal medullary chromaffin cells.

Isolated adrenal medullary chromaffin cells maintained in culture have been widely used to study neurosecretory events. Many of these studies have been conducted using cells obtained from the bovine adrenal. In this study we have cultured chromaffin cells from an alternative large animal model, the deer, and have conducted the first characterization of secretion from this preparation. Cervine chromaffin cells, preloaded with [3H]noradrenalin, displayed a strong secretory response to the cholinergic agonist carbachol, with a maximal secretion of approximately 28% cell content over 15 min. This response was reproduced by nicotinic but not muscarinic agonists and was similarly inhibited by nicotinic but not muscarinic antagonists. Nicotine-evoked secretion measured over a 15 min time period was inhibited approximately 50% by the L-type Ca2+-channel antagonist nifedipine and approximately 20% by N-type (omega-conotoxin GVIA) or N, P/Q-type (omega-conotoxin MVIIC) antagonists. In contrast the response was unaffected by omega-agatoxin IVA, a P/Q-type antagonist. In addition to nicotinic receptor stimulation, activation of PACAP or histamine H1 receptors resulted in a concentration-dependent increase in secretion. PACAP was approximately two-fold more effective than histamine although both were weaker secretagogues than nicotine. In contrast, cervine chromaffin cells did not respond to angiotensin II or bradykinin, two agents known to stimulate secretion from bovine chromaffin cells. These data provide an initial characterization of the secretory response from cervine adrenal medullary chromaffin cells indicating that there are marked similarities but also potentially significant differences between them and their far more extensively described bovine counterparts.

The involvement of specific phospholipase C isozymes in catecholamine release from digitonin permeabilized bovine adrenal medullary chromaffin cells.

The role of phospholipase C (PLC) in exocytosis has been investigated using digitonin permeabilized, [(3)H]noradrenaline ([(3)H]NA) loaded, bovine adrenal medullary chromaffin cells. The PLC inhibitor U-73122 caused a concentration-dependent suppression of Ca(2+)-evoked [(3)H]NA release but increased basal release (that occurring in the absence of Ca(2+)). Preincubation with antibodies against PLCgamma1 or PLCbeta3 (but not PLCdelta1, delta2, beta1 and beta2) also inhibited [(3)H]NA release evoked by Ca(2+) and increased basal release, indicating that only specific PLC isozymes are involved in these actions. Interestingly, PLCgamma1 (but not PLCbeta3) antibodies inhibited the ability of Ca(2+) to increase PLC activity in these permeabilized cells. These data therefore suggest that PLCgamma1 activity may have a specific role in regulating the exocytotic response from the adrenal chromaffin cell.