Somatostatin sst₂ receptors inhibit peristalsis in the rat and mouse jejunum

Abstract

Somatostatin [somatotropin release-inhibitory factor (SRIF)] has widespread actions throughout the gastrointestinal tract, but the receptor mechanisms involved are not fully characterized. We have examined the effect of selective SRIF-receptor ligands on intestinal peristalsis by studying migrating motor complexes (MMCs) in isolated segments of jejunum from rats, mice, and sst 2-receptor knockout mice. MMCs were recorded in 4-to 5-cm segments of jejunum mounted horizontally in vitro. MMCs occurred in rat and mouse jejunum with intervals of 104.4 Ϯ 10 and 131.2 Ϯ 8 s, respectively. SRIF, octreotide, and BIM-23027 increased the interval between MMCs, an effect fully or partially antagonized by the sst2-receptor antagonist Cyanamid154806. A non-sst2 receptor-mediated component was evident in mouse as confirmed by the observation of an inhibitory action of SRIF in sst2 knockout tissue. Blocking nitric oxide generation abolished the response to SRIF in rat but not mouse jejunum. sst2 Receptors mediate inhibition of peristalsis in both rat and mouse jejunum, but a non-sst2 component also exists in the mouse. Nitrergic mechanisms are differentially involved in rat and mouse jejunum. knockout; migrating motor complex; enteric nervous system; somatotropin release-inhibitory factor ISOLATED SEGMENTS OF BOWEL can perform complex and coordinated contractile activity, which is dependent on interactions between myogenic and local neural mechanisms. The polarized reflex responses to intestinal stimuli, first described by Bayliss and Starling (3), are now recognized to involve activation of ascending and descending enteric pathways leading to contraction and relaxation of smooth muscle (6). A variety of different transmitters and neuromodulators in these enteric pathways contributes to the coordination of this peristaltic activity. Somatostatin [somatotropin release-inhibitory factor (SRIF)] is present in a subpopulation of descending interneurones that project caudally within the myenteric plexus but not into either the longitudinal or circular muscle layers of the intestine (10,31,35). SRIF is also found in submucous plexus neurones, around submucosal blood vessels, and is present in mucosal endocrine cells in human (31), guinea pig (10), and rodent intestine (12, 13). SRIF is released by intestinal distension (11) and participates in the coordination of descending relaxation (21). The effects of exogenous SRIF on intestinal motility are complex. In the guinea pig ileum, both excitatory and inhibitory effects, operating through prejunctional mechanisms (14,18,24,36,45), have been described. The contractile response of the rat colon to SRIF also appears to involve activation of noncholinergic nerves (33), possibly by a process of disinhibition of vasoactive intestinal peptide (VIP) ergic/nitrergic interneurones supplying longitudinal muscle motoneurones (22). In contrast, the activity of VIPergic/nitregic neurons supplying the circular muscle layer is augmented by SRIF leading to relaxation (21). Thus SRIF plays a neuromodulat...

Effect of Conjugated Bile Salt Taurodeoxycholic Acid (TDCA) on Mice Colonic Motor Activity

“…The experiment was performed according to Abdu et al (14,15); mice were sacrificed by cervical dislocation, colon segment was rapidly excised and placed in gassed (95% O 2 and 5% CO 2 ) Krebs bicarbonate buffer solution (composition in mM: 117 NaC1, 4.7 KC1, 25 NaHCO 3 , 2.5 CaCl 2 , 1.2 MgCl 2 , 2 NaH 2 PO 4 , 1.2 H 2 O, and 11 D-glucose), cleared of mesenteric connective tissue, and the lumen was flushed with Krebs solution. Colon segment was prepared and mounted horizontally in separate 20-ml perfusion chambers.…”

Effect of cholic acid on colonic motility in mice

“…Muscles tissue segments were cleared of any mesenteric connective tissue and the lumen flushed with Krebs solution. Tissues were prepared according to the method described by Abdu et al (2002). Colon segments approximately 5 cm in length were prepared from each animal (four in total) and were mounted horizontally in separate 20 ml perfusion chambers.…”

Purinergic mechanisms in the control of gastrointestinal motility

“…However, recent developments allow some conclusions to be drawn. Isolated mouse intestine and colon exhibit periodic strong contraction complexes that propagate along the segment in a manner analogous to phase III contractions of interdigestive MMCs [132][133][134][135]. This similarity is so strong that the colonic propagating contraction complexes are usually termed colonic MMCs, although they may actually be analogues of mass-movement contractions involved in defecation.…”