Is desensitization of intestinal 5-hydroxytryptamine receptors an in-vitro phenomenon?

The responses of proximal jejunum and distal ileum to successive applications of 5-hydroxytryptamine (5-HT) were examined in-vitro and in-vivo by measuring the electrical changes that reflect the stimulation of Cl- secretion. In stripped intestinal sheets the second application of a maximal concentration of 5-HT failed to elicit any response, indicating that complete desensitization had occurred. If submaximal concentrations were used, a second response was observed, although it was smaller than the first, indicating partial desensitization. Replacing the bathing solutions following application of a maximal 5-HT concentration also reduced, but did not abolish, the degree of desensitization observed with a second application of 5-HT. In an in-vivo preparation, however, there was no diminution of the responses to four successive maximal doses of 5-HT. This lack of desensitization was also evident in the cardiovascular responses to 5-HT. It is concluded that desensitization to 5-HT is a phenomenon that is readily observed only in-vitro and which is probably related to the inability of a small amount of isolated tissue to eliminate 5-HT.