Somatostatin: regulation of secretion.

Somatostatin is released in the blood, in synaptic clefts, and in the intercellular space in response to a variety of stimuli. In view of its multiple functions, various sites of synthesis and release, and rapid inactivation, as well as extremely low levels of somatostatin in the peripheral blood, somatostatin can hardly be considered to be a hormone whose target is reached via the general circulation. The target organs of cells may be located near the somatostatin-producing cells and can be reached via local circulation such as the hypophyseal portal system and the microportal circulation in the gut mucous membrane. Somatostatin released from the neurons acts as a hypophyseotropic hormone and a neurotransmitter or neuromodulator. Furthermore, somatostatin may also act in a paracrine fashion by being released into the intercellular space. This space may sometimes be compartmentalized by tight junctions so that the action of the peptide is limited only to the adjacent cells. In this fashion, the pancreatic islet somatostatin influences nearby A- and B- cell activities. Gut D cells, prototypes of APUD or paraneuron cells, show considerable similarity to neurosecretory cells not only in biochemical processes but also morphologically. While the somatostatin neurons in the brain respond to dopaminergic and catecholaminergic agonists, D cells in the gut respond to chemical stimuli in the lumen by sensing them with microvilli. They release somatostatin into the blood stream, into the intercellular space, and into the gastric and intestinal lumen. Luminal somatostatin may affect other endocrine and nonendocrine cells in the mucous membrane of the gut. It is noted that the same stimulatory agent does not always stimulate somatostatin release from different organs; one agent stimulates the release from one organ and suppresses release from the other organ.