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...

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Context:Doxorubicin (DOX) and gemcitabine (GEM) are anticancer drugs that were combined in a nanoemulsion (NE) to reduce their adverse side effects.Aim:To detect the antitumor activity of the combination formulas of GEM and DOX, loaded either in water (GEM+DOX-Sol) or in NEs (GEM–DOX combination/loaded NE [GEM+DOX/LNE]), in female Swiss albino mice inoculated with Ehrlich ascites carcinoma (EAC).Settings and Design:The anticancer assessment of the NE formulas was implemented in 200 mice, which were divided into 10 groups.Materials and Methods:It includes the detection of the change in body weight, analysis of the hematological and serum biochemical profiles, and study of the histopathologic alterations of the heart tissues.Statistical Analysis:One-factor analysis of variance was used.Results:Mice treated with GEM + DOX/LNE, which have an z-average of 155.38±2.33nm and zeta potential of −38.5±1.3 mV, recorded a considerable improvement in the mean survival time (MST), which was 60 days, as compared to the EAC control group, which has an MST of 28 days. It also restored the hematological and serum biochemical parameters toward normal values.Conclusions:The combination of GEM and DOX in NE has significantly diminished the cardiotoxicity of DOX and hematotoxicity of GEM while improving their antitumor properties.

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