Olasmaa M, Guidotti A, Costa E
Fidia-Georgetown Institute for the Neurosciences, Georgetown University, Washington, DC 20007.
Mol Pharmacol. 1992 Mar;41(3):456-64.
The possibility that vasoactive intestinal polypeptide (VIP) may facilitate the nicotine-mediated induction of adrenal medullary tyrosine hydroxylase (TH) was investigated with primary cultures (5-7 days in vitro) of bovine adrenal chromaffin (BAC) cells. Exposure of BAC cells to 100 microM nicotine led to only a marginal increase in the amount of TH mRNA, TH protein, and TH activity. VIP, alone or in the presence of a phosphodiesterase inhibitor, produced a marked increase in TH mRNA, TH protein, and TH activity. Moreover, VIP together with nicotine, at concentrations that alone were devoid of effect, increased the amount of TH mRNA and TH activity. A synergistic effect of VIP and nicotine on cAMP accumulation in BAC cells was also apparent. The marginal effects of large doses of nicotine on both cAMP accumulation and TH induction were blocked completely by hexamethonium but were also partially inhibited by the VIP antagonist [p-chloro-D-Phe6,Leu17]-VIP. Nicotine may, therefore, stimulate the release of VIP from cultured BAC cells and VIP, in turn, by increasing cAMP, may synergize with nicotine to enhance TH gene expression.
利用牛肾上腺嗜铬（BAC）细胞的原代培养物（体外培养5 - 7天），研究了血管活性肠肽（VIP）是否可能促进尼古丁介导的肾上腺髓质酪氨酸羟化酶（TH）的诱导。将BAC细胞暴露于100微摩尔的尼古丁仅导致TH mRNA、TH蛋白和TH活性的少量增加。单独使用VIP或在磷酸二酯酶抑制剂存在的情况下，TH mRNA、TH蛋白和TH活性显著增加。此外，VIP与尼古丁共同作用时，在单独使用时无效的浓度下，增加了TH mRNA的量和TH活性。VIP和尼古丁对BAC细胞中cAMP积累的协同作用也很明显。大剂量尼古丁对cAMP积累和TH诱导的微弱作用被六甲铵完全阻断，但也被VIP拮抗剂[p - 氯 - D - Phe6，Leu17] - VIP部分抑制。因此，尼古丁可能刺激培养的BAC细胞释放VIP，而VIP反过来通过增加cAMP，可能与尼古丁协同作用以增强TH基因表达。
