title: Reflex splanchnic nerve stimulation increases levels of proenkephalin A mRNA and proenkephalin A-related peptides in the rat adrenal medulla.
abstract: The effect of reflex splanchnic nerve stimulation on proenkephalin A biosynthesis was investigated in the rat adrenal medulla. Tissue levels of native [Met5]enkephalin-like immunoreactivity (IR) (measured by direct RIA of tissue extracts), cryptic [Met5]enkephalin-like IR (calculated as the increase in [Met5]enkephalin-like IR detected in tissue extracts after sequential digestion with trypsin and carboxypeptidase B), and proenkephalin A mRNA were determined in adrenal medulla from rats sacrificed at various times after a period of insulin-induced hypoglycemia. Two hours of insulin hypoglycemia, which produced intense reflex stimulation of the splanchnic nerves as evidenced by a 55% decrease in the adrenal medulla catecholamine levels, resulted in a 3-fold increase in proenkephalin A mRNA levels in this tissue. The proenkephalin A mRNA levels reached a maximum 15-fold increase over control values 24 hr after this period of hypoglycemic stress and then gradually declined with an approximate half-life of 4 days. Native and cryptic [Met5]enkephalin-like IR had increased 9-fold and 12-fold, respectively, 24 hr after this period of hypoglycemia, and both demonstrated maximum increases of 130-fold and 50-fold, respectively, after 96 hr. Combined pretreatment (i.p. administration) with the ganglionic and muscarinic blocking agents chlorisondamine (5 mg/kg of body weight) and atropine (1 mg/kg) blocked the increase in levels of proenkephalin A mRNA seen in the rat adrenal medulla following insulin hypoglycemia. These data indicate that reflex splanchnic nerve discharge stimulates proenkephalin biosynthesis, probably at the level of gene expression.
mesh_terms: D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism*; D007003:Hypoglycemia / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009693:Nucleic Acid Hybridization; D010276:Parasympatholytics / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012018:Reflex; D013153:Splanchnic Nerves / Q000502:physiology*
chemical_list: D002395:Catecholamines; D004745:Enkephalins; D007328:Insulin; D010276:Parasympatholytics; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D004744:Enkephalin, Methionine