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A reduction in core body temperature is one of the characteristic consequences of 5-HT1A receptor activation in rodents. In this study, we characterized the hypothermic effects of four 5-HT1A receptor ligands with varying affinity and selectivity at the 5-HT1A receptor. 8-OH-DPAT and flesinoxan (full agonists); ipsapirone (selective partial agonist) and eltoprazine (non selective partial agonist), all induced a dose-dependent reduction in core body temperature, which was maximal 30 min subsequent to administration. This response differed quantitatively between the agonists, in both the extent and the duration of its effects. The selective 5-HT1A receptor antagonist WAY 100635 (0.15 mg/kg), attenuated the hypothermia induced by the partial agonists, ipsapirone (10 mg/kg) and eltoprazine (10 mg/kg). In contrast, the higher dose of WAY 100635 (1 mg/kg) antagonized the effects of all agonists. This study therefore further confirms the utility of hypothermia as a simple, robust in-vivo probe of 5-HT1A receptor function. This paradigm, which was enhanced by use of specific antagonists such as WAY 100635, may prove useful for the detection and characterization of novel 5-HT1A receptor ligands.

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SUMMARY Because of the possible clinical association between coeliac disease and sarcoidosis, the incidence of humoral sensitivity to dietary proteins was examined in patients with sarcoidosis. Raised concentrations of circulating IgG antibodies to alpha gliadin were found in 41/99 sarcoid patients whereas antibody levels to casein, beta lactaglobulin and ovalbumen were similar to normal controls. Subsequently, a group of 26 sarcoid patients were selected for small intestinal biopsy; 11 had raised and 15 normal alpha gliadin antibody (AGA) levels. One AGA positive patient had villous atrophy consistent with coeliac disease. Intraepithelial lymphocyte (IEL) counts were raised in AGA positive (median 30; 95% confidence limits 22-46) and AGA negative (median 24; 95% confidence limits 19-32) sarcoid patients when compared with a control group (median 13.5; 95% confidence limits 10-18) p<001. Serum IgG concentrations were raised in 11/52 patients tested but there was no correlation between IgG levels and the presence ofIgG antigliadin antibodies. HLA Dr typing was done in 21 of the 26 biopsied patients. The coeliac disease associated antigen Dr3 was present in eight of 21 (38%) which is very similar to the prevalence in unselected blood donors (34%). There was no significant difference in IEL counts between Dr3 positive and Dr3 negative sarcoid patients. These findings suggest that in patients with sarcoidosis, there is an altered gastrointestinal mucosal immune response, accompanied in about 40% of patients by specific sensitisation to wheat protein.

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