Mononuclear-cell peptide mediation of chromaffin-cell epinephrine secretion.
Previously, we have shown that novel mononuclear-cell-derived factor(s) [molecular weight (MW) < 3,000] stimulate the release of epinephrine (EPI) from adrenal medullary chromaffin cells to levels comparable to that of maximal cholinergic stimulation. The present study provides evidence that the observed bioactivity is due to the action of a single peptide of 627 Da apparent MW. The peptide nature of the bioactive component was suggested by a decreased bioactivity after acid hydrolysis as well as altered bioactivity subsequent to peptidase (carboxypeptidase Y, leucine aminopeptidase) treatment. The bioactive conditioned-medium (CM) peptide(s) were isolated and further characterized using SDS-PAGE analysis. SDS-PAGE separation of G-25 Sephadex purified CM shows that bioactivity resides in a single peptide band. Additional studies revealed that CM also mediates norepinephrine release from sympathetic ganglia cells. Regulation of peptide production was shown to involve negative feedback in that incubation with mononuclear cells with EPI prevented further bioactive peptide release. This feedback inhibition was partially blocked by the beta-adrenergic receptor antagonist propranolol. These findings suggest a novel and potentially important mechanism by which the immune system can alter neuroendocrine function.
Roberts
J C
JC
Department of Physiology, Loyola University Medical Center, Maywood, Ill. 60153, USA.
Mathews
H L
HL
DePotter
W
W
Pinxteren
J
J
Jones
S B
SB
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004837:Epinephrine / Q000378:metabolism*; D005246:Feedback; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000502:physiology*; D008970:Molecular Weight; D015213:Neuroimmunomodulation; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012636:Secretory Rate; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
D000319:Adrenergic beta-Antagonists; D017077:Culture Media, Conditioned; D010455:Peptides; D011433:Propranolol; D007770:L-Lactate Dehydrogenase; D004837:Epinephrine