Peripheral 5‐HT 4 receptors

Abstract

The 5‐HT 4 receptor is a member of the seven transmembrane spanning G‐protein‐cou‐pled family of receptors. The receptor is positively coupled to adenylate cyclase and exists in two iso‐forms (5‐HT 4 S and 5‐HT4L) that differ in the length and sequence of their carboxy termini. The 5‐HT 4 receptor is pharmacologically defined by selective agonists such as SC 53116 and RS 67506, and selective antagonists such as GR 113808, SB 204070, and RS 39604. The receptor is widely distributed in the central nervous system and peripheral tissues. In the periphery, the receptor plays an important role in the function of several organ re‐sponses including the alimentary tract, urinary bladder, heart and adrenal gland. In the alimentary tract, stimulation of 5‐HT 4 receptors has a pronounced effect on smooth muscle tone, mucosal electrolyte secretion, and the peristaltic reflex. In the urinary bladder, activation of 5‐HT 4 receptors modulates cholinergic/purinergic transmission. In the heart, stimulation of atrial 5‐HT 4 receptors produces positive inotropy and tachycardia that can precipitate arrythmias. In the adrenal gland, agonism of 5‐HT 4 receptors stimulates release of Cortisol, corticos‐terone, and aldosterone. Since its discovery in 1988, significant advances have been made in our understanding of the physiology and pharmacology of the 5‐HT 4 receptor. These advances have led to the development of several selective 5‐HT 4 receptor agonists and antagonists that may have therapeutic utility in the treatment of peripheral disorders such as irritable bowel syndrome, gastroparesis, urinary incontinence and cardiac arrhythmias.—Hegde, S. S., Eglen, R. M. Peripheral 5‐HT 4 receptors. FASEB J. 10, 1398‐1407 (1996)