ABSTRACT
It is perhaps fitting that the seminal work on 5-HT receptor classification was performed using the guinea pig ileum. 1 In this tissue, 5-HT was shown to have two distinct effects. The first effect was a direct activation of ileal smooth muscle that was sensitive to blockade by phenoxybenzamine (dibenzyline); the receptor mediating this effect was termed the D receptor. The second effect was a neuronally mediated contraction of smooth muscle that was sensitive to blockade by both atropine and morphine. The receptor mediating this cholinergically transducted event was termed the M receptor. This classification endured for almost 20 years, before the development of radioligands allowed the clear identification of two distinct 5-HT receptors. 2 The subsequent development of selective agonists and antagonists facilitated a detailed pharmacological analysis of the receptors for 5-HT and allowed the construction of a classification that accommodated the 5-HT1 and 5-HT2 receptors of Peroutka and Snyder, as well as the D and M receptors of Gaddum and Picarelli. 3 It is a continuation of this process that lead to the most recent nomenclature. 4 It is around this framework that the 5-HT receptors present in the gut will be identified and characterized in this chapter.
