Central actions of somatostatin-28 and oligosomatostatin agonists to prevent components of the endocrine, autonomic and visceral responses to stress through interaction with different somatostatin receptor subtypes

Abstract

Somatostatin was discovered four decades ago and since then its physiological role has been extensively investigated, first in relation with its inhibitory effect on growth hormone secretion but soon it expanded to extrapituitary actions influencing various stressresponsive systems. Somatostatin is expressed in distinct brain nuclei and binds to five somatostatin receptor subtypes which are also widely expressed in the brain with a distinct distribution pattern. The last few years witnessed the discovery of highly selective peptide somatostatin receptor agonists and antagonists representing valuable tools to delineate the respective pathways of somatostatin signaling. Here we review the centrally mediated actions of somatostatin and related selective somatostatin receptor subtype agonists to influence the endocrine, autonomic, and visceral components of the stress response and basal behavior as well as thermogenesis.

Fig. 1

Acute stress-induced endocrine (stimulation of ACTH, inhibition of GH), behavioral (reduction of food intake), autonomic (stimulation of sympathetic outflow) and visceral (delayed gastric emptying and stimulation of propulsive colonic motor function) alterations. These responses are all antagonized by central injection of somatostatin agonists except the stress-related suppression of GH which is mediated by hypothalamic somatostatin. Differential somatostatin receptor subtypes are involved in the various anti-stress responses. Light gray: stimulation, black: inhibition.