We examined the in vitro effects of neurotransmitters, high KCl as well as sialic acid-containing compounds (GM1; SC) on transglutaminase (TG) activity in isolated superior cervical ganglia (SCG) one week after denervation or axotomy. Following denervation, TG activity in SCG decreased to 83% of the unoperated control value, whereas that of axotomized ganglia was 28% of control. Thus, TG activity was relatively unaffected when sympathetic ganglionic neurons were preserved, but was markedly reduced under conditions where neurons were degenerating. Addition of ACh (0.1 mM) to the medium during aerobic incubation stimulated TG activity more than 3-fold in denervated ganglia but had no effect on TG activity in axotomized ganglia. Similarly, the NE (0.05 mM)-induced decrease of TG activity observed in intact SCG was also seen following denervation (-49%) but not following axotomy. In denervated SCG, the stimulatory effects of ACh were virtually abolished by co-addition of the cholinergic antagonists, atropine or hexamethonium, while the suppressant effects of NE were blocked by the adrenergic antagonists, propranolol, prazosin or yohimbine. These results imply that transmitter-induced rapid changes in TG activity occur predominantly in ganglionic neurons. When the ganglia were depolarized by high KCl (50 mM), a significant increase in TG activity in each intact, denervated and axotomized SCG was seen with qualitatively similar manner, suggesting that high KCl-induced depolarization affects both neuronal and glial components in the SCG. The marked increase in ganglionic TG activity in response to GM1 (5 nM) and synthetic SC (0.02 mM) were lost in denervated SCG but only partially reduced in axotomized SCG.(ABSTRACT TRUNCATED AT 250 WORDS)