Structural bases of vasopressin/oxytocin receptor functionreview
Аннотация: The neurohypophyseal hormones vasopressin and oxytocin are two closely related nonapeptides, synthesized mainly by the magnocellular neurons of the hypothalamus. Their peptide sequences differ only in the amino acids at positions 3 and 8, but, for both hormones, the formation of a disulfide bond between Cys residues at the 1 and 6 positions results in a peptide constituted of a 6 amino acid cyclic part and a 3 amino acid C-terminal part. Both peptides exert various hormonal effects. Circulating oxytocin is mostly known for its ability to elicit the contraction of uterine smooth muscle at term and that of myoepithelial cells that surround the alveoli of the mammary gland during lactation. The main endocrine functions of arginine vasopressin (AVP) are the facilitation of water reabsorption by the kidney and the contraction of smooth muscle cells in arteries. AVP released in the portal blood in the median eminence acts as a potent secretagogue of adrenocorticotropin. In addition, it has become clear that vasopressin and oxytocin, besides mediating well-documented functions at the periphery, are also critically involved in numerous central processes including higher cognitive functions such as memory and learning (see Barberis & Tribollet 1996 for review). Vasopressin and oxytocin were the first biologically active peptides to be synthesized. This achievement, by Du Vigneaud and coworkers, 40 years ago, ushered in the modern era of peptide chemistry. During the subsequent decades, many structural analogues of the neurohypophyseal hormones have been synthesized and pharmacologically characterized (Manning & Sawyer 1993). Peripheral vasopressin and oxytocin receptors have been classified on the basis of both the second messenger system coupled to the receptors and the affinity of a series of vasopressin and oxytocin analogues with enhanced selectivity for a certain receptor type. These classification criteria have led to the distinction of V1a vasopressin (liver, smooth muscle cells from blood vessels, and most peripheral tissues expressing vasopressin receptors), V1b vasopressin (adenohypophysis), V2 vasopressin (kidney) and oxytocin (uterus, mammary gland) receptors ( Jard et al. 1988). To date central receptors have been identified as being of the vasopressin V1a and oxytocin subtypes. Moreover, a great number of molecular probes have been developed, including agonists and antagonists, and radiolabelled, fluorescent or photosensitive ligands. These make this receptor family a good model with which to study structure–function relationships. Today, the four different receptor subtypes have been cloned in mammals, lower vertebrates and invertebrates. Molecular cloning studies have renewed interest in these neurohormone receptors. Vasopressin V1b receptor mRNA has been detected in peripheral tissues (kidney, thymus, heart, lung, spleen, uterus and breast) and numerous areas of the brain in the rat (Lolait et al. 1995), and this receptor subtype has also been characterized in rat adrenal (Grazzini et al. 1996). These studies suggest that the vasopressin V1b receptor may serve additional and unknown functions in the brain and at the periphery. The primary focus of this review is to summarize recent studies that have led to novel insights into the molecular bases of vasopressin and oxytocin receptor functions.
Год издания: 1998
Авторы: Claude Barberis, Bernard Mouillac, Thierry Durroux
Издательство: Bioscientifica
Источник: Journal of Endocrinology
Ключевые слова: Neuroendocrine regulation and behavior, Neuroscience of respiration and sleep, Neonatal Respiratory Health Research
Другие ссылки: Journal of Endocrinology (PDF)
Journal of Endocrinology (HTML)
PubMed (HTML)
Journal of Endocrinology (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 156
Выпуск: 2
Страницы: 223–229