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Nerve growth factor synthesis in cultured rat iris: Modulation by endogenous transmitter substances

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Abstract

Organ cultures of rat iris show a characteristic change in the levels of both nerve growth factor (NGF) and its mRNA: a rapid but transient initial increase is followed by a smaller but persistently elevated NGF synthesis. This time course may be influenced by release of a factor(s) from degenerating nerve terminals and/or by the lack of some factor(s) repressing NGF synthesis in vivo. We therefore analyzed the influence of biogenic amine transmitter substances and putative neuropeptides on this elevation of NGF synthesis in cultured iris. The marked increase of NGF synthesis seen initially in culture was not completely mimicked by any of the substances tested. A specific increase in NGF production up to 150 % of control was observed only with cGMP. We also obtained some evidence that reaction to trauma following the culture procedure could enhance NGF production: cutting of hides into small pieces increased NGF production in culture up to 250% of control and, vice versa, treatment with 1 μM dexamethasone decreased NGF production to about 60 % of control. However, the sympathetic neurotransmitter norepinephrine (NE) decreased both NGF and its mRNA levels specifically in a dose-dependent manner (0.01-1 mM) to a minimum of about 25% of control. In situ hybridization with mRNANGF-specific probes showed that in cultures of dissociated iris cells all cells were capable of expressing mRNANGF, but that 0.1 mM NE preferentially decreased expression of mRNANGF in smooth muscle cells. Thus, our results indicate that the sympathetic transmitter NE is capable of downregulating NGF synthesis in the target cells of sympathetic neurons.

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      In fact, there are numerous studies showing that adrenergic agonists can increase NGF production in astroglial cells [69,70], vascular smooth muscle cells [71] and some lines of immortalized fibroblasts [70]. In contrast to this evidence, there are other reports sustaining that NE decreases NGF protein and mRNA levels in a dose-dependent manner in the iris [72] and brown adipose tissue [73]. Even more contradictory data come from studies on cardiac physiopathology: scientists are divided on the question of whether NE induces or inhibits NGF production.

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    1

    R. Hellweg is a fellow of the Max-Planck-Society.

    2

    Current address: California Institute of Technology, Division of Biology, Pasadena, CA 91125.

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