Functional significance of neuronal and extraneuronal transmitter uptake in rat salivary glands. The effect of protriptyline and normetanephrine.

Abstract

The effect of normetanephrine (NM) on effector cell response to noradrenaline (NA) in vivo and on extraneuronal amine uptake in vitro has been investigated in rat submaxillayr glands. Tissue slices were incubated with 3H-NA and the metabolic pattern of the radioactivity in the slices as well as of the efflux from the slices was analyzed. The level of extraneuronally retained radioactive material was found to be markedly reduced at a NM concentration of 20 μg/ml after inhibition of neuronal uptake by protriptyline (PTP). In the presence of an intact neuronal membrane pump mechanism 200 μg/ml of NM also reduced the level of radioactive material, indicating that NM has an inhibitory effect on extraneuronal and in higher concentration also on neuronal uptake and retention of NA and its metabolites. NM was found to markedly potentiate the secretory response to NA in vivo, when doses of NA larger than 1 μg were used. At lower NA doses there was no difference between NM pretreated and control rats. When neuronal uptake was prevented by pretreatment with PTP, NM was found to potentiate the secretory response to NA over the entire dose range. Inhibition by PTP of neuronal uptake only did not affect the dose-response curve for NA and data are presented which indicate that the absence of such a potentiation is due to a decreased salivary gland blood flow induced by NA after PTP pretreatment. The increased responses recorded after NM could not be ascribed to an additive effect of this amine, since NM was found to be a very weak α-receptor agonist in the rat submaxillary gland; doses of more than 1000 μg i.v. were needed to detect a secretory response. The data indicate that the extraneuronal uptake of the transmitter has a functional significance in the rat submaxillary gland by reducing high transmitter concentrations in the vicinity of the receptors.