Adrenergic re-innervation of smooth muscle of nictitating membrane by preganglionic sympathetic fibres.

1. The preganglionic and post-ganglionic trunks of the cervical sympathetic nerve were joined in an end-to-end anastomosis after excision of the superior cervical ganglion in the cat.2. Seventy-five days after the anastomosis the diameter of the pupil was nearly normal and there was almost complete recovery of the prolapsed palpebra and of the nictitating membrane. The contraction of the nictitating membrane, induced by electrical stimulation, caudally to the point of anastomosis, showed that the smooth muscle of the nictitating membrane had been re-innervated.3. Neither hexamethonium nor nicotine had any marked effect on the contraction of the nictitating membrane. Severing the regenerated nerve trunk produced a degeneration contraction. These results are strong evidence that the denervated membranes were re-innervated by true cholinergic preganglionic fibres.4. Our pharmacological studies indicated that in the re-innervated preparations neuromuscular transmission was adrenergic in the sense that it was blocked by phentolamine and not by atropine. These results were confirmed by the histochemical-fluorescence studies which showed that the endings of the regenerated axons contained high concentrations of catecholamines.5. Electron microscopy showed that the regenerated terminals contained none of the small dense-core vesicles, considered to be typical of adrenergic nerve endings, but contained clear synaptic vesicles and an unusually great number of large granular vesicles.6. Our results suggest that the denervated nictitating membranes were re-innervated by cholinergic presynaptic sympathetic fibres that had been modified so that they could release catecholamines in addition to, or instead of, acetylcholine.