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Redistribution of axonal enzymes as a function of time in vitro was studied in an unbranched segment of frog sciatic nerve. Cholinesterase activity moved peripherally at a rate of 99 mm/day and centrally at 19 mm/day. One-quarter of the total nerve content of the enzyme was estimated to be in motion, one-eighth in each direction. Mitochondrial enzymes (hexokinase and glutamic dehydrogenase) moved peripherally at 20-31 mm/day, centrally at 11-20 mm/day. Only 10% of the total content of these mitochondrial enzymes was in motion. No movement of choline acetylase or 6-phosphogluconic dehydrogenase activity was seen even after 4 days in vitro. However, in a 12 day in vivo experiment choline acetylase moved toward the periphery at a rate of 0.34 mm/day. After a day or so in vitro the distal accumulations of cholinesterase and glutamic dehydrogenase decreased, with a concomitant and quantitatively equivalent increase in enzyme activities at the proximal end of the nerve. It is postulated that during incubation a mechanism for reversing the direction of flow develops in the peripheral stump of the nerve. Vinblastine inhibited central and peripheral flow of both cholinesterase and glutamic dehydrogenase. Movement of cholinesterase was not affected by ouabain, thalidomide, or phenobarbital, nor by K+ excess (110 mM) or absence.

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Nerve growth factor has been quantified by both bioassay and radial immunodiffusion in mouse saliva elicited by several secretagogues. The concentrations by bioassay of nerve growth factor in both epinephrine-and norepinephrine-induced saliva (3400 and 900 gg/ml, respectively) are higher than reported in any other source. In contrast, the concentrations of nerve growth factor in isoproterenol-and pilocarpine-induced saliva are relatively low (17 and 2 ;sg/ml, respectively). The specific activity of the salivary nerve growth factor was 41, 36, 2, and 0.6 ;&g/mg of protein in secretions elicited by epinephrine, norepinephrine, pilocarpine, and isoproterenol, respectively. Salivation after administration of either epinephrine or norepinephrine was completely inhibited by the a-adrenergic blocker, phenoxybenzamine. These results suggest that the release of saliva rich in nerve growth factor is primarily regulated through a-adrenergic receptors.The submaxillary gland of male mice is the richest known source of nerve growth factor (NGF) (1-3). Venom of numerous species of snakes (4, 5) and the submaxillary glands of female mice (2, 3) are also rich sources of NGF. Since snake venom is the secretory product of the venom gland, the phylogenetic homologue of the manmalian salivary gland, early investigators also looked for NGF in mouse saliva. reported that pilocarpine-induced mouse saliva contained detectable levels of biologically active NGF, but estimated the concentration to be at least 5000 times lower than in salivary gland extracts. Those studies only examined saliva induced by a parasympathetic secretagogue, despite the fact that salivary secretions are also elicited by activity of the sympathetic nervous system. Such adrenergic secretions differ from cholinergic saliva in both protein concentration and composition (7,8).Several lines of evidence suggest that NGF might be secreted from the submaxillary gland after adrenergic stimulation. This growth factor is concentrated in the convoluted granular tubules (9, 10) with a number of other proteins that are secreted by the gland: (i) renin (or isorenin) (11, 12), (ii) esteroproteases (13; 14), and (iii) epidermal growth factor (EGF) (15,16 In the present paper and in an earlier abstract (18), we report exceedingly high NGF concentrations in salivary secretions elicited by epinephrine or norepinephrine, but not by isoproterenol or pilocarpine. The high NGF concentrations in both epinephrine-and norepinephrine-induced salivas have been quantified by both bioassay and radial immunodiffusion. NGF release was inhibited by the a-adrenergic blocker, phenoxybenzamine. Thus, a secretion rich in NGF that is both biologically active and immunologically reactive is selectively released by the action of adrenergic agonists on a-receptors within mouse salivary glands.MATERIALS AND METHODS Saliva was collected from 10-to 16-week-old male mice. The animals were anesthetized with pentobarbital, 60 mg/kg. Salivation was usually induced by the intraperitoneal injection of sec...

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