No abstract

Injection of the antidepressant desmyethylimipramine (DMI, 10 mg/kg) into intact rats or into rats in which the superior cervical ganglia had been decentralized caused a marked enhancement of the swimming stress-induced increase in pineal gland acetyl-CoA:serotonin N-acetyltransferase (N-acetyltransferase, EC 2.3.1.5) activity. DMI is known to block uptake, the transport of catecholamines by nerve endings. It was found that DMI had no effect on enzyme activity in superior cervical ganglionectomized (SCGX) rats which were swimming stressed. The pineal glands of these animals are devoid of nerve endings. In unstressed intact or unstressed surgically altered rats, injection of DMI caused only a minor increase in N-acetyltransferase activity, which was much smaller than that seen after stress. After 5 h in organ culture sympathetic nerve endings within the pineal gland are still intact. At this time DMI treatment of pineal glands taken from intact rats shifted the dose-response curve for epinephrine (EPI) stimulation of N-acetyltransferase activity by two orders of magnitude, but caused only a slight change in the dose-response curve for isoproterenol, which is not taken up into nerve endings. In contrast, DMI treatment in organ culture had no effect on the dose-response curve for EPI in denervated pineal glands. These results support the hypothesis that the response of pineal N-acetyltransferase activity to stimulation by stress is influenced by uptake. It would appear that in addition to terminating neuronal adrenergic transmission, this transport process physiologically protects the pineal gland against nontranssynaptic adrenergic stimulation.

No abstract

Abstract— Crude mitochondrial fractions prepared from rat brains took up l‐tryptophan. The component of the crude mitochondrial fraction responsible for this uptake is the synaptosome. After uptake of tryptophan occurred, rupture of synaptosomes released 97 per cent of the tryptophan unchanged. Rupture of synaptosomes abolished uptake. Penetration of the limiting membrane of synaptosomes by l‐tryptophan both as influx and efflux was studied. Uptake of l‐tryptophan was rapid, temperature dependent, partially inhibited by cyanide, 2‐deoxy‐d‐glucose and ouabain, but apparently unaffected by low external sodium ion concentrations. d‐tryptophan was a poor inhibiteur of l‐tryptophan uptake. Concentration gradients Internal: external of up to 4:1 were achieved. Kinetic studies on l‐tryptophan uptake and its competitive inhibition by l‐phenylalanine indicated a saturable carrier‐mediated transport system, present in the rat at birth. l‐Tryptophan efflux from preloaded synaptosomes was markedly stimulated by certain arrino acids and its influx stimulated by preloading with l‐tryptophan. This countertransport is further evidence for carrier‐mediated or facilitated diffusion. On the basis of countertransport data there seem to be at least two systems for transporting amino acids across synaptosomal membrane. The relevance of these studies to the role of l‐tryptophan as the initial precursor of brain 5‐hydroxytryptamine is examined.