Abstract

Fifteen to 22 hours after removal of the superior cervical ganglion, the submaxillary gland of the rat showed a period of transient activity. The time course of the degeneration secretion coincided with that of the decline of the endogenous levels of norepinephrine in the gland. Previous parasympathetic decentralization enhanced the transient secretory activity observed after sympathetic denervation. In vitro studies of uptake and metabolism of ³H-norepinephrine showed that 15 hours after sympathetic denervation the total uptake and the neuronal accumulation of the tritiated amine was decreased to about 50% of the control values. A further reduction was obtained 24 hours after ganglionectomy. Intraneuronal metabolism of ³H-norepinephrine to ³H-3,4-dihydroxyphenylglycol was reduced to the same extent as the uptake of the amine. Cocaine inhibited both accumulation and intraneuronal metabolism of ³H-norepinephrine in cotrols and in glands 15 hours after denervation while it had no effect 24 hours after sympathectomy. Studies on the retention and metabolism of ³H-norepinephrine showed that the amine was less efficiently retained in the glands 15 hours after denervation than in the control glands. During the spontaneous outflow of the amine from denervated glands, a marked reduction in the intraneuronal metabolism was obtained. This phenomenon coincided with an increased formation of extraneuronal metabolites of the ³H-amine. The sensitivity of denervated glands to exogenous norepinephrine was determined after treatment with reserpine. Fifteen hours after sympathectomy, the dose-response curves to norepinephrine were shifted to the left by 0.3 log unit, while 24 hours or 21 days after surgery, the shift was 0.6 log unit. The administration of cocaine potentiated the secretory responses to norepinephrine in the controls and to a lesser extent in glands 15 hours after denervation while it had no effect 24 hours after denervation. It is concluded that after sympathetic denervation the reduction in the neuronal uptake and in the intraneuronal metabolism of norepinephrine contribute to the development of the degeneration secretion because a higher proportion of the released transmitter can reach the receptors in the unmetabolized form.