RESUMO
Despite our knowledge of somatostatin (SOM) in gastrointestinal functions, little information is available on the SOM receptors (SSTRs) mediating these effects. This study focussed on the expression of SSTRs in non-inflamed and Schistosoma mansoni-infected murine ileum using immunocytochemistry, reverse transcriptase (RT)-PCR and quantitative real time RT-PCR (qPCR). In the non-inflamed ileum, SSTRs showed a widespread, cell-type specific expression pattern. For instance, SSTR2A immunoreactivity was detected in a minor population of submucous but not myenteric glial cells. In the inflamed ileum, significant changes in the expression pattern of SSTRs occurred, with SSTR1 and SSTR3 expression on mucosal mast cells (MMCs) and mucosal nerve fibres. SSTR4-immunoreactive nerve fibres were detected in granulomas and the lamina propria. qPCR experiments indicated significantly increased mRNA levels for SOM, SSTR1 and SSTR3 in inflamed ileum. This study reveals that SSTRs are expressed in specific cell types in murine ileum. Expression of SSTR1 and SSTR3 on MMCs and increased density of SOM-expressing nerve fibres in the lamina propria during inflammation, support the hypothesis that SOM is implicated in the physiological control of MMCs during intestinal inflammation. Evidence is provided that in mouse mainly SSTR1, SSTR3 and SSTR4 are involved in the somatostatinergic inflammatory effects during intestinal schistosomiasis.
Assuntos
Ileíte/fisiopatologia , Ileíte/parasitologia , Receptores de Somatostatina/genética , Schistosoma mansoni , Esquistossomose mansoni/fisiopatologia , Animais , Sistema Nervoso Entérico/imunologia , Sistema Nervoso Entérico/metabolismo , Sistema Nervoso Entérico/fisiopatologia , Ileíte/imunologia , Íleo/imunologia , Íleo/metabolismo , Íleo/parasitologia , Imuno-Histoquímica , Mastócitos/imunologia , Mastócitos/parasitologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Receptores de Somatostatina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/metabolismo , Somatostatina/metabolismoRESUMO
We recently described the widespread expression of somatostatin (SOM) receptors (SSTRs) in the non-inflamed and inflamed murine ileum. Surprisingly, no significant changes were observed in the SSTR2 expression during intestinal inflammation. These data, combined with several recent independent lines of investigation, raised some question about the long presumed central role of SSTR2 in the SOM-mediated effects in the physiological and pathological activity of the gastrointestinal (GI) tract. To further unravel the role of SSTR2 in GI physiology, we studied the expression of SOM and SSTRs in the normal and inflamed SSTR2 knockout/lacZ knockin (SSTR2(-/-)) ileum. The SSTR2(-/-) ileum was characterized by a widespread distribution of multiple SSTR subtypes in non-inflamed and inflamed conditions. Moreover, the absence of SSTR2 did not induce any compensatory effect in the distribution pattern or expression level of any of the other SSTR subtypes. In contrast, the amount of SOM mRNA was significantly lower in SSTR2(-/-) ileum than that in wild type animals. Quantitative analysis revealed a decreased number of SOM-expressing neurons in both enteric plexuses of the knockout animals, implying a possible link between the number of SOM-expressing enteric neurons and the expression of SSTR2 in the enteric nervous system. In conclusion, these data show that a reconsideration of the role of SSTR2 in the GI somatostatinergic effects is in order and further corroborate recent data on the role of other SSTR subtypes in the inflammatory effects of SOM during intestinal inflammation.