Somatostatin sst2 receptor-mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat

Background & Aims: Octreotide inhibits visceral sensations in clinical studies, but the site of action and the receptor type(s) involved are unknown. Our aim was to investigate the effects of octreotide, the selective SSt(2) receptor agonist (BIM 23027), and the SSt(2) antagonist (Cyanamid154806) on the activity of mesenteric afferent fibers innervating the rat jejunum. Their effects were investigated on baseline discharge, mechanosensitivity, and responses to algesic chemicals. Methods: Extracellular multiunit recordings of jejunal afferent nerve firing were made in pentobarbitone-anesthetized (60 mg/kg intraperitoneally) male Wistar rats. Results: Octreotide and BIM23027 (0.001-100 mug/kg intravenously) each evoked a long-lasting inhibition of baseline discharge, which was blocked by cyanamid:154806 (3 mg/kg) and absent in chronically vagotomized animals. Afferent responses to bradykinin were also inhibited by an SSt(2) receptor-mediated mechanism but were unaffected by vagotomy. Ramp distentions of the jejunum evoked a biphasic activation of afferent nerve discharge, the low threshold component of which was attenuated in vagotomized animals. SSt(2) receptor agonists significantly inhibited the mechanosensitivity of spinal, but not vagal, afferents. Conclusions: These data suggest that activation of somatostatin SSt(2) receptors inhibit populations of mesenteric afferents likely to be involved in nociceptive transmission.