Schwarzschild M A, Zigmond R E
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
J Neurochem. 1991 Feb;56(2):400-6. doi: 10.1111/j.1471-4159.1991.tb08165.x.
Previous studies have shown that certain peptides of the secretin-glucagon family stimulate tyrosine hydroxylase activity in sympathetic neurons of the superior cervical ganglion and three of its end organs, i.e., the iris, pineal gland, and submaxillary gland. To determine whether a similar regulation occurs in other sympathetic neurons, the effects of two of these peptides, secretin and vasoactive intestinal peptide, were examined in the right cardiac ventricle of the rat, a tissue innervated primarily by the middle and inferior cervical ganglia. Both peptides stimulated tyrosine hydroxylase activity, measured in situ, in this tissue. In addition, several second messenger systems were investigated as possible mediators of this peptidergic stimulation of tyrosine hydroxylase activity in autonomic end organs. 8-Bromoadenosine 3',5'-cyclic monophosphate and forskolin elevated tyrosine hydroxylase activity in slices of both the right ventricle and the submaxillary gland. 8-Bromoguanosine 3',5'-cyclic monophosphate also stimulated tyrosine hydroxylase activity in both tissues, whereas nitroprusside stimulated activity only in the submaxillary slices. Furthermore, the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine and/or Ro 20-1724 potentiated the stimulation by secretin, as well as the stimulations by forskolin and nitroprusside. Phorbol 12,13-dibutyrate also stimulated tyrosine hydroxylase activity in cardiac and submaxillary slices; however, no potentiation of these effects was seen following addition of either phosphodiesterase inhibitor. These data, taken together with those of previous studies, suggest a role for a cyclic nucleotide, probably adenosine 3',5'-cyclic monophosphate, in the peptidergic stimulation of tyrosine hydroxylase activity in sympathetic nerve terminals.
先前的研究表明，促胰液素 - 胰高血糖素家族的某些肽可刺激颈上神经节及其三个终末器官（即虹膜、松果体和下颌下腺）的交感神经元中的酪氨酸羟化酶活性。为了确定其他交感神经元中是否发生类似的调节，研究了其中两种肽，即促胰液素和血管活性肠肽，对大鼠右心室的影响，右心室主要由颈中神经节和颈下神经节支配。这两种肽均刺激了该组织中酪氨酸羟化酶的活性（原位测量）。此外，还研究了几种第二信使系统，作为自主终末器官中这种肽能刺激酪氨酸羟化酶活性的可能介质。8 - 溴腺苷3',5'-环磷酸和福斯可林提高了右心室和下颌下腺切片中的酪氨酸羟化酶活性。8 - 溴鸟苷3',5'-环磷酸也刺激了这两种组织中的酪氨酸羟化酶活性，而硝普钠仅刺激了下颌下腺切片中的活性。此外，磷酸二酯酶抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤和/或Ro 20 - 1724增强了促胰液素的刺激作用，以及福斯可林和硝普钠的刺激作用。佛波醇12,13 - 二丁酸酯也刺激了心脏和下颌下腺切片中的酪氨酸羟化酶活性；然而，添加任何一种磷酸二酯酶抑制剂后均未观察到这些作用的增强。这些数据与先前研究的数据一起表明，环核苷酸（可能是腺苷3',5'-环磷酸）在交感神经末梢肽能刺激酪氨酸羟化酶活性中起作用。
