The addition of retinoic acid (RA, 50 nM) to Dulbecco's modifed Eagle's medium containing 1.0% bovine serum albumin and 50 mu g/l of gentamicin markedly increased the activity of a Ca2+-dependent tissue transglutaminase (TGase) (ca. 3.2-fold), which stabilizes newly formed protein assemblies at the sites of synapses, in isolated rat superior cervical sympathetic ganglia (SCG), which is abundant in synapses, following in vitro aerobic incubation for 3 h at 37 degrees C. An isomer of RA, 13-cis-RA (50 nM), showed the same tendency but rather lesser magnitude (ca. 1.7-fold) in ganglionic TGase activation. Also, retinal (50 nM), a precursor of RA, had a little effect on TGase-stimulation (ca. 1.5-fold) in SCG. The RA-induced enhancement of ganglionic TGase activity was completely eliminated in the presence of either actinomycin D (1.0 mu g/ml), a depressant of molecular transcriptional activity, or a potent inhibitor of protein synthesis, cycloheximide (10 mu g/ml). Kinetic analyses show that the stimulation of ganglionic TGase activity evoked by RA addition was associated with only an increase in V-max value (ca. 3.3-fold) without change in K-m value. Thus, the enzyme protein of TGase might be synthesized de novo in the ganglia in response to RA. The RA-induced activation effect of ganglionic TGase almost disappeared (ca. 1.3-fold) 1 week following denervation, by which time preganglionic cholinergic nerve terminals were degradated. In axotomized SCG, where sympathetic neurons were degenerated and reactive proliferation of glial cells was in progress, the RA-evoked increase in ganglionic TGase activity was attenuated (ca. 1.3-fold). These findings imply that some retinoids, especially RA effectively participate in the cholinergic potentiation of synaptic activity.
