Peptide regulation of adrenal medullary function

The discovery of peptides in the splanchnic nerve and adrenal gland, and their co-existence with conventional neurotransmitters raises questions about their possible functional roles in catecholamine (CA) secretion and gene transcription in the adrenal gland. Short-term, stress-induced CA secretion is regulated biphasically by substance P (SP) which inhibits acetylcholine (ACh) action at SP greater than 10(-6) M and facilitates CA secretion in response to metabolic and physical stressors, ACh or electrical stimulation at SP less than 10(-6) M. Long-term, gene transcription of phenylethanolamine-N-methyltransferase (PNMT) is exerted by glucocorticoids, and gene transcription of Proenkephalin-A by agents such as histamine, angiotensin II and VIP that increase cyclic AMP (cAMP). The final products of these two genes, adrenaline and Met-enkephalin and congeners, are co-stored in chromaffin granules of adrenaline cells but gene expression of these products is clearly under differential control.