Somatostatin release

In the trans Golgi compartment the peptide is sorted via secretory vesicles into a regulated pathway. In contrast to vesicles of the constitutive pathway, vesicles of the regulated pathway are stored in the cytoplasm until their stimulated release. Membrane depolarisation as well as a wide range of substances such as intracellular mediators, neuropeptides, neurotransmitters, classical hormones, cytokines, growth factors, ions and nutrients induce somatostatin secretion. General inhibitors of somatostatin release are opiates, GABA, leptin and TGF- 3. 

When the gastritis induced by H. pylori is confined to the antrum, the increase of gastrin and the reduction of somatostatin released by the G and D cells in the antrum, respectively, will increase the drive for acid secretion from the preserved oxyntic mucosa [45]. This increased... 

In the mouse, whereas no evidence of H3 receptors was found in isolated gastric glands (Muller et al., 1993), in the whole stomach, (R)a-methylhistamine actually increased, and thioperamide decreased acid secretion, thus indicating a definite stimulatory role for H3 receptors in this species (Table 2). Apparently, this excitatory effect, which contrasts with the observations obtained in other models, was due to an inhibitory effect on somatostatin release from fundic D cells (Schubert et al., 1993 Vuyyuru and Schubert 1993). Also, an inhibitory effect on somatostatin secretion mediated by H3 agonists was observed in other species (rat and dog). However, contrarily to what might have been expected, in these species, the inhibitory effect on somatostatin is not followed by an increase in acid secretion, but it is instead followed by a decrease, owing to the predominant H3-mediated inhibition on the release of excitatory mediators (histamine, acetylcholine) from other sites (ECL, cholinergic nerve terminals)... 

Figure 3. Effect of N -methylhistamine produced by Helicobacter pylori on acid secretion On the one hand, this compound may reduce acid secretion by inhibiting, via H3 receptor activation, histamine synthesis and release from ECL cells on the other hand, FI3 receptor activation on D cells, with consequent inhibition of somatostatin release, may increase acid secretion. Additionally, direct activation of H2 receptors on parietal cell by N -metylhistamine must also be considered (this mechanism is not shown in the scheme).

Bado, A., Moizo, L., Laigneau, J.P., Delwaide, J., Lewin, M.J.M., 1994. H3-receptor regulation of vascular gastrin and somatostatin releases by the isolated rat stomach. Yale J. Biol. Med. 67, 113-121. 

Bonanno G, Raiteri M, Emson PC (1988) In vitro release of somatostatin from cerebral cortical slices Characterization of electrically-evoked release. Brain Res 447 92-7 Bonanno G, Gemignani A, Schmid G et al (1996) Human brain somatostatin release from isolated cortical nerve endings and its modulation through GABAb receptors. Br J Pharmacol 118 ... 

FIGURE 4.5 Influence of lecithin amount added to glyceryl tripalmitate (Dyn 116) on somatostatin release (particles washed with bidestilled water). (Adapted from [37] with permission from Elsevier.)... 

The secretagogues for somatostatin are similar to those that cause secretion of insulin. The metabolites that increase somatostatin release include glucose, arginine, and leucine. The hormones that stimulate somatostatin secretion include glucagon, vasoactive intestinal polypeptide (VIP), and cholecystokinin (CCK). Insulin, however, does not directly influence somatostatin secretion. 

Fig. 43.2. Control of growth hormone secretion. Various factors stimulate the release of GHRH from the hypothalamus. The hypothalamus also releases somatostatin in response to other stimuli. GHRH stimulates and somatostatin inhibits the release of growth hormone from the anterior pituitary. Growth hormone causes the release of IGF-I from liver and other tissues. IGF-I inhibits GHRH release and stimulates somatostatin release.

Capdevila, ]., Chacos, N., Falck, J.R., Manna, S., Negro-Vilar, A. and Ojeda, S.R. (1983). Novel hypothalamic arachidonate products stimulate somatostatin release from the median eminence. Endocrinology, 113, 421-423... 

Herrmann, J. and R. Bodmeier (1995). The effect of particle microstructure on the somatostatin release from poly(lactide) microspheres prepared by a W/OAV solvent evaporation method. Journal of Controlled Release 36(1-2) 63-71. 

The peptide is released from both fundic and antral D cells. The latter are more numerous. Somatostatin release is used almost universally as a downregulator of cellular function and, therefore, although a peptide, must have a short half-life to ensure organ specificity. This allows classification of this inhibitor as a paracrine mediator of add secretion. 

The exact source of somatostatin acting on the oxyntic mucosa has been a matter of some debate, because cells containing somatostatin-D cells-are present both in the antrum and in the oxyntic mucosa. Additionally, postganglionic nerve fibers in the submucosa contain somatostatin, which may act as a neural transmitter. Because mucosal D cells, both in the antrum and in the fundus, possess elongated basal processes, somatostatin released locally may function as a paracrine regulator. 

Because somatostatin is so widespread in its distribution, there is some difficulty in assigning an origin for somatostatin released into the circulation. Gastrin and CCK both stimulate somatostatin release from isolated D cells, and this cell type has both CCK, and CCKz receptors. 

Because CCK stimulates acid secretion in vitro through release of histamine from ECL cells but inhibits add secretion in vivo, it is likely that the inhibitory action in vivo is due to somatostatin release driven by CCK, activation. 

Peptides of the secretin/VIP family stimulate somatostatin release, and the consequent suppression of gastrin release may account for at least some of the ability of such peptides to inhibit acid secretion in vivo. PACAP, when injected in vivo, inhibits gastrin-stimulated acid secretion this is probably due to stimulation of the fundic D cell at a VIP receptor. When somatostatin-neutralizing antibody is given along with PACAP, acid secretion ensues due to the effect of PACAP on the ECL cell being revealed. 

In contrast to the other cells in the gastric mucosa, the D cell has inhibitory muscarinic receptors of either the M or WL, subtype, allowing the conclusion that vagal stimulation of acid secretion inhibits somatostatin release. 

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