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The aim of this study was to obtain more information regarding the ‘atypical’ 5-HT₇ receptor of the rat jejunum. 5-HT₇-induced contractions of the jejunum were elicited by 5-HT in the presence of ondansetron. Maximal responses were slightly larger in tissues from male compared to female rats of comparable age, with E_max values of 97.2 ± 3.3 and 84.25 ± 4.3% respectively compared to acetylcholine as an internal standard. However, the pEC₅₀ valuesfor 5-HT were not significantly different. The mRNA expression levels of the 5-HT₇ receptor were similar in whole jejunum and longitudinal muscle tissues taken from males and females. It was also shown that the maximal response of the jejunum from male rats was larger than the responses from mid intestine and ileum. However, in female tissues, the E_max of the mid intestine was significantly larger than the ileum, but not different from the jejunum. The results provide further insights into the ‘atypical’ 5-HT₇ receptor of the rat jejunum and are also useful in optimising the preparation for further studies.

The rat isolated jejunum was used as a functional model to screen some antidepressant drugs at the ‘atypical’ 5-HT₇ receptor. Mianserin acted as a surmountable antagonist of 5-CT with a pA₂ value of 8.22 ± 0.33. The apparent pK_B of maprotiline against 5-CT was 7.67 ± 0.24 at 100 nmol/l, but higher concentrations suppressed the maxima. An apparent pK_B could not be obtained for amitriptyline, because 10 nmol/l reduced the E_max of 5-CT without causing parallel displacement. Higher concentrations of 30 and 100 nmol/l caused further suppressions. Amoxapine, loxapine and desipramine (each at 100 nmol/l) caused similar effects, suppressing the E_max values to 5-HT by approximately 50%, while lower concentrations failed to cause parallel displacements. These results further extend the activity profiles of the drugs investigated.

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