Laminin increases both levels and activity of tyrosine hydroxylase in calf adrenal chromaffin cells.
We have investigated the effects of substrate-bound laminin on levels of enzymes of the catecholamine biosynthetic pathway in primary cultures of calf adrenal chromaffin cells. Laminin increases the levels of the enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl-transferase. This effect is selective, in that levels of other enzymes (lactate dehydrogenase, aromatic amino acid decarboxylase, and acetylcholinesterase) are not increased. The effect of laminin can be blocked by antibodies directed against a fragment of the heparin-binding domain of the molecule, whereas antibodies directed against other fragments do not block the increase in tyrosine hydroxylase. Thus the laminin domain involved in enzyme regulation in chromaffin cells is apparently the same as that previously implicated in laminin's interactions with neurons to potentiate survival and stimulate neurite outgrowth (Edgar, D., R. Timpl, and H. Thoenen, 1984, EMBO (Eur. Mol. Biol. Organ.) J., 3:1463-1468). The increase in chromaffin cell tyrosine hydroxylase levels is preceded by an activation of the enzyme in which the Vmax (but not the Km) is altered. The effects of laminin appear to be developmentally regulated, since neither activation nor increased levels of tyrosine hydroxylase occur in adult adrenal chromaffin cells exposed to laminin.
Acheson
A
A
Edgar
D
D
Timpl
R
R
Thoenen
H
H
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D007158:Immunologic Techniques; D007679:Kidney Medulla / Q000166:cytology / Q000201:enzymology*; D007797:Laminin / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D007797:Laminin; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D010455:Peptides; C008973:polyornithine; D014446:Tyrosine 3-Monooxygenase