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Cysteamine-Induced Depletion of Brain Somatostatin Is Associated with Up-Regulation of Cerebrocortical Somatostatin Receptors^*

Fraser Laboratories, McGill University, Departments of Medicine, Neurology and Neurosurgery, Royal Victoria Hospital, and Montreal Neurological Institute Montreal, Quebec H3A, 1A1, Canada

Address correspondence and requests for reprints to: Dr. C. B. Srikant, Room M3-06, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec H3A 1A1 Canada.

Abstract

Cysteamine (CSH) administered as a single sc injection to rats produced rapid depletion of cerebrocortical Somatostatin-14 like immunoreactivity (S-14 LI) with a significant 48% reduction occurring within 5 min and maximum (72%) decrease at 4 h. The depletion of S-14 LI was associated with a 1.7 fold increase in B_max of the cerebrocortical S-14 receptors 5 min after CSH administration and a concomitant but slower increase in the affinity of these receptors [dissociation constant (Kd) being 1.8- and 1.6-fold lower than the control at 30 and 60 min, respectively, post CSH]. Incubation of intact synaptosomes with 1 mM CSH at 37 C in vitro for 60 min also caused a rapid depletion of S-14 LI, but in contrast to the in vivo data, there was no change in the B_max or Kd of the S-14 receptors for up to 30 min beyond which time a 2.8-fold decrease in the affinity of S-14 receptors was observed. Higher concentrations of CSH (10 mM) added during the incubation of synaptosomes in vitro completely abolished the specific binding of these receptors. The pituitary S-14 receptors were studied 30 min after CSH administration and unlike the cerebrocortical S-14 receptors at this time did not exhibit any change in B_max or affinity. When added at the time of the binding assay CSH (1 mM) was without a direct effect on cerebrocortical as well as pituitary membrane S-14 receptors. Furthermore, addition of CSH at the time of binding assay did not destroy the integrity of [¹²⁵I-Tyru]S-14. It is concluded that 1) administration of CSH to rats in vivo depletes brain S-14 LI and up-regulates synaptosomal S-14 receptors. 2) Exposure of synaptosomes to CSH in vitro for 30 min also depletes S-14 LI but has no effect on S-14 receptors suggesting that S-14 receptor regulation by S-14 is an in vivo phenomenon or requires the intact cell. 3) CSH has a direct inhibitory effect on S-14 receptor binding after prolonged in vitro incubation. 4) Pituitary S-14 receptors unlike those in the brain are unaffected by S-14 LI depletion at least acutely. (Endocrinology 115: 990–995, 1984)

Footnotes

^* This work was supported by Grants MT 6832 and MT 6196 from the Canadian Medical Research Council and USPHS Grant AM-21373. Presented at the Annual Meeting of the Canadian Society for Clinical Investigation, Calgary, Alberta, September 1983.

Received December 20, 1983.

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