Cysteamine-induced depletion of brain somatostatin is associated with up-regulation of cerebrocortical somatostatin receptors
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 Bmax of the cerebrocortical S-14 receptors 5 min after CSH administration and a concomitant but slower increase in the affinity of these receptors. 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 there was no change in the Bmax 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 (greater than or equal to 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 Bmax 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 (/sup 125/I-Tyr11)S-14. It is concluded that administration of CSH to rats in vivo depletes brain S-14 LI and up-regulates synaptosomal S-14 receptors. Exposure of synaptosomes to CSH in vitro for 30 min also depletes S-14 LI but has no effect on S-14 receptors. CSH has a direct inhibitory effect on S-14 receptor binding after prolonged in vitro incubation. Pituitary S-14 receptors unlike those in the brain are unaffected by S-14 LI depletion at least acutely.
- Research Organization:
- McGill Univ., Montreal, Quebec, Canada
- OSTI ID:
- 6204507
- Journal Information:
- Endocrinology; (United States), Vol. 115:3
- Country of Publication:
- United States
- Language:
- English
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