Acetylcholine nicotinic receptor subtypes in chromaffin cells.

Abstract

In the adrenal gland, acetylcholine released on stimulation of the sympathetic splanchnic nerve activates neuronal-type nicotinic receptors (nAChRs) in chromaffin cells and triggers catecholamine secretion. At least two subtypes of nAChRs have been described in bovine chromaffin cells. The main subtype, a heteromeric assembly of α3, β4 and perhaps α5 subunits, is involved in the activation step of the catecholamine secretion process and is not blocked by the snake toxin α-bungarotoxin. The other is α-bungarotoxin-sensitive, and its functional role has not yet been well defined. The α7 subunit conforms the homomeric structure of this subtype. All nAChR subunits share the same molecular organization and structural data at atomic resolution level are now available for some homomeric and heteromeric ensembles. The α3, β4 and α5 subunits are clustered in genomes of different species, with the transcription factor Sp1 playing a co-ordinating role in the transcriptional regulation of these three subunits. The transcription factor Egr-1 controls the differential expression of α7 nAChR in adrenergic chromaffin cells, as happens with the enzyme phenylethanolamine N-methyl transferase. For unknown reasons, whole cell currents observed in bovine chromaffin cells clearly differ of the ones observed when different combinations of subunit RNAs are injected in oocytes. In addition to the typical nicotinic ligands, a variety of unrelated substances with clinical relevance can target nAChRs in chromaffin cells and, therefore, affect catecholamine secretion. They can act as agonists, antagonists or allosteric modulators.