Receptors in the gastrointestinal tract

Abstract

The receptor concept has been recently evolved and a new science was actually created, namely "receptorology". Receptors are now identified by means of different techniques (binding, agonist-antagonist interaction, autoradiography, etc.) The new techniques allowed the investigators to define new receptors and new subtypes of the "classical" ones. In the gastrointestinal (GI) tract a number of receptors have been identified and localized both on the effector organ and in the nerbe terminal where they exert an important modulatory function on the neurotransmitter release. Recent biochemical studies have allowed a better understanding of the post-receptor event involving the second or third messenger regulation. Particular changes of receptors were recognized and they allow us to consider receptors not as static entities but as very dynamic components of the plasma membrane capable of different kinds of alterations, like interconversion, internalization, mobility, up- and downregulation, etc. Together with the "classical" receptors (cholinergic, adrenergic, opioid, etc.) also new receptors were identified: different subtypes of receptors for the tachykinins, for prostaglandin of the E type in the gastric parietal cell and the so-called dihydropyridine (DHP) receptor in the calcium channel of different areas of the gut. It is obvious that the precise knowledge of receptors and of their agonists and antagonists will represent the basis for a more specific and efficacious treatment of various gastrointestinal disorders. The receptor concept, introduced at the beginning of this century by J. N. Langley (1906) ("....It is convenient to have a term for the specially excitable constituent and I have called it receptive substance..."), progressively developed up to a complete definition and in some cases actually to a chemical identification of a series of different receptors (for review see Ariens, 1983; 1984). In spite of the new techniques and the recent acquisitions on the matter, many doubts still exist about the definition and the methods to be preferred for the identification of new receptor subtypes. Pharmacologists are particularly fond of the study of agonist-antagonist interaction, biochemists trust better binding studies, whereas other investigators claim that the new autoradiographic technique must be preferred (for review see Barlow, 1986). In particular cases desensitization techniques have been employed (Schild, 1973); in addition it seemed also useful to apply the criterion of the different localization or that of the different post-receptor events to characterize particular receptor subtypes. All of these methods have advantages and disadvantages; in a recent meeting ("Towards the classification of hormone receptors", London, Dec. 1985), these were emphasized by different investigators. Sentences like "binding and grinding" or like "everything binds to everything" give an idea of the appreciation of binding techniques by some investigators; on the other hand, agonists and/or antagonists were claimed not to be always available or not to be sufficiently specific; considering the post-receptor event, different receptors may activate the same effector system, but the opposite is also true, since a single receptor may activate different coupling systems (Table 1). In conclusion, the problem of the identification of new receptors is still an open problem and of course only when the use of different techniques will lead to the same results, we will be sure of the reliability of the methods. © 1987.