Pituitary adenylate cyclase activating polypeptide (PACAP) potently enhances tyrosine hydroxylase (TH) expression in adrenal chromaffin cells.
In primary cultured bovine adrenal chromaffin cells (BACC), pituitary adenylate cyclase activating polypeptide 1-38 (PACAP) produced a dose related increase in tyrosine hydroxylase (TH) Vmax when measured 48 hours after the beginning of the treatment; a significant increase was observed with 0.5 nM and the maximal induction of close to 2.5-fold was found with 0.1 microM PACAP. The potency of PACAP was nearly 3 orders of magnitude greater than forskolin and VIP in inducing TH activity. These effects were preceded by an increase in TH mRNA levels, that started 2 hours after treatment and peaked 12 hours later. The presence of the phosphodiesterase inhibitor HL 725 further increased the stimulation of TH activity by PACAP, indicating that this activation was mediated via a cascade of events initiated by cAMP. Nicotine (1 microM) failed to increase TH activity significantly, however, when added in association with PACAP, a statistically significant increase of TH was elicited with peptide concentrations 5 times lower (0.1 nM) than the threshold dose of the peptide. The stimulation of nicotinic receptors facilitates the TH induction elicited by PACAP.
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Fidia-Georgetown Institute for the Neurosciences, Georgetown University, Washington, DC 20007.
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Costa
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D000313:Adrenal Medulla / Q000166:cytology*; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002838:Chromaffin System / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D007546:Isoquinolines / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D044005:Tetrahydroisoquinolines; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D007546:Isoquinolines; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D009538:Nicotine; C035964:trequinsin; D014446:Tyrosine 3-Monooxygenase