The somatostatin receptor family

Increase in substance P and CGRP, but not somatostatin content of innervating dorsal root ganglia in adjuvant monoarthritis in the rat

Somatostatin (SS), a peptide of 14 amino acids, is a hydrophobic molecule. Its multiple physiological effects derive from its binding to an outer membrane receptor. This chapter will focus on the characterization of SS binding sites, their coupling with multiple second messenger systems, their localization and their multiple functions. Finally, we shall briefly review the evidence for the possible involvement of SS receptors in brain pathology.

Somatostatin Receptors in the Central Nervous System

Glucocorticoids can differentially regulate somatostatin (SRIH) receptor subtype expression depending on the duration of treatment, dose used and tissue type examined. In order to determine if glucoco

Role of Glucocorticoids in the Regulation of Pituitary Somatostatin Receptor Subtype (sst1–sst5) mRNA Levels: Evidence for Direct and Somatostatin-Mediated Effects

Early efforts to identify the hypothalamic stimulating factor for growth hormone (GH) release from the pituitary inadvertently resulted in the discovery of a hypothalamic inhibitor of GH release [57]. Despite initial skepticism regarding its existence, this inhibiting factor, somatostatin (SS; also called somatotropin release-inhibiting factor, SRIF), was subsequently isolated and structurally characterized by Brazeau et al. [17]. As has been true for most of the brain neuropeptides identified over the last two decades, the known neuroregulatory effects of the tetradecapeptide SS have expanded far beyond its originally discovered role. The possibility that alterations in SS might reflect or contribute to the pathophysiology of disorders of the central nervous system (CNS) was first examined by Patel et al. in 1977 [75]. Subsequently, a variety of reports appeared describing decreased SS in brain and/or cerebrospinal fluid (CSF) of patients with several neuropsychiatric disorders, particularly Alzheimer’s disease and depression. These studies of SS in neuropsychiatric disorders will be reviewed in this chapter, as will the evidence supporting a role for SS as a modulator of CNS activity.

Somatostatin in neuropsychiatric disorders.

The effects of adrenalectomy on somatostatin (SS) concentration and specific binding in cerebral cortex, hippocampus, striatum, and hypothalamus were examined using [125I-Tyr11]SS as the binding ligand. Adrenalectomy did not affect the concentration of SS-like immunoreactivity in the brain areas studied. Nevertheless, the number of SS receptors was significantly decreased in membrane preparations from hippocampus, striatum, and hypothalamus, but not in cerebral cortex. No significant differences in the apparent binding affinity values were seen after adrenalectomy. The adrenalectomy-induced decreases in [125I-Tyr11]SS receptors were completely reversed by glucocorticoid replacement with dexamethasone. These results demonstrate that adrenalectomy modulates SS receptors in discrete brain areas, suggesting the existence of a possible relationship between corticosteroids and SS in the neuronal activity of these structures. The physiological significance of these findings remains to be clarified.

Maria Nelly Rodriguez

Papers

Decrease in Number of Somatostatin Receptors in Rat Brain After Adrenalectomy: Normalization After Glucocorticoid Replacement*