Somatostatin receptor agonists found

Figure 15.33. Somatostatin receptor agonists found through combinatorial chemistry.

Growth hormone. Mood disorders have been related to alterations in the activity of the growth-hormone axis. A blunted growth-hormone response to clonidine, an a2 receptor agonist, has been consistently found in depression. Increased growth-hormone secretion during the day and decreased nocturnal growth-hormone secretion have also been observed in depressed patients. Depressed patients have lower CSF concentrations of somatostatin, compared to those with schizophrenia and normal controls. While lower CSF somatostatin is a state-dependent marker of depression, it occurs in a number of unrelated nonpsychiatric conditions, and thus appears to be relatively nonspecific. 

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)... 

Not many nonpeptide agonists are yet available, but such compounds have been described — for example, in the angiotensin, CCK, and opioid receptor systems. In fact, for a few receptors, such as the somatostatin, ghrelin, and complement C5A receptors, basically all compounds found by screening using binding assays are agonists. In contrast, for the majority of receptors for which... 

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