Somatostatin sst(2) receptor-mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat

Background & Aims: Octreotide inhibits visceral sensations in clinical stud ies, 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. Th eir effects were investigated on baseline discharge, mechanosensitivity, an d responses to algesic chemicals. Methods: Extracellular multiunit recordin gs of jejunal afferent nerve firing were made in pentobarbitone-anesthetize d (60 mg/kg intraperitoneally) male Wistar rats. Results: Octreotide and BI M23027 (0.001-100 mug/kg intravenously) each evoked a long-lasting inhibiti on of baseline discharge, which was blocked by cyanamid:154806 (3 mg/kg) an d absent in chronically vagotomized animals. Afferent responses to bradykin in were also inhibited by an SSt(2) receptor-mediated mechanism but were un affected by vagotomy. Ramp distentions of the jejunum evoked a biphasic act ivation of afferent nerve discharge, the low threshold component of which w as attenuated in vagotomized animals. SSt(2) receptor agonists significantl y inhibited the mechanosensitivity of spinal, but not vagal, afferents. Con clusions: These data suggest that activation of somatostatin SSt(2) recepto rs inhibit populations of mesenteric afferents likely to be involved in noc iceptive transmission.