Vasopressin and Oxytocin Receptors
| Title: | Vasopressin and Oxytocin Receptors |
|---|---|
| Author: | Zingg, Hans H. |
| Publisher: | Baillieres Clinical Endocrinology and Metabolism |
| Date Published: | January 01, 1996 |
| Reference Number: | 38 |
The oxytocin and the vasopressin V1a, V1b and V2 receptors have recently been cloned and shown to form a sub-family within the large superfamily of G-protein-linked receptors. Renal V2 receptors mediate vasopressin-induced water reabsorption via induction of intracellular cAMP production in collecting duct cells. Most remaining actions of vasopressin on blood vessel constriction, liver glycogenolysis, platelet adhesion, adrenal angiotensin II secretion and certain brain functions are mediated via v1a-type receptors that are coupled to a Gq/11 protein. V1 receptor activation leads to stimulation of phospholipases C, D and A2 and an increase in intracellular calcium. Vasopressin stimulates pituitary corticotrophin release via a third vasopressin receptor type (V1b) which is present on corticotrophs. Oxytocin induces myometrial contraction, endometrial prostaglandin F2 alpha production, mammary gland milk ejection, renal natriuresis and specific sexual, affiliative and maternal behaviours via oxytocin receptors which are also coupled to a Gq/11 protein. Although only one oxytocin receptor type has been cloned so far, recent binding studies indicate that uterine endometrial oxytocin receptors may constitute a distinct receptor subtype. In contrast to most other membrane receptors, the expression of oxytocin receptors undergoes very rapid and physiologically relevant up-and-down-regulation. A greater than 100-fold up-regulation of uterine oxytocin receptors occurs during gestation and may represent the trigger for parturition. Indeed, oxytocin receptor antagonists are able to counteract preterm labour and may soon be available for clinical use. The presence of oxytocin receptors on breast cancer cells and the growth-inhibitory effects of OT suggest a potential use of oxytocin analogues for breast cancer treatment. Whereas no mutations of the oxytocin or V1a or V1b receptors have been found, over 60 different genetic mutations of the (renal) V2 receptor have been described which represent the cause for congenital nephrogenic diabetes insipidus.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
VP and OT have similar structures but perform different roles. In mammals, VP helps maintain fluid homeostasis, induces a number of processes such as constricting blood vessels and blood clotting, and helps temperature, memory and learning processes. OT stimulates milk ejection, uterine contraction, prostaglandin production, sperm transport, and a number of other functions. These hormones could do none of these things without their respective receptors.
VP receptors (VPRs) are divided into two main subclasses: V1 and V2 receptors. Each has a different function and often different, but not always mutually exclusive, locations. V1 receptors are present in the liver, vascular smooth muscle cells, brain, blood, central nervous system and the kidneys, where they bind with vasopressin to initiate a series of different processes in blood vessels, the liver, adrenals and the brain.V2 receptors are present in the distal tubules and collecting ducts of the kidney where they accept the message of the hormone vasopressin and start the urine concentrating process.
It is unclear at this time whether more than one type of OT receptors (OTRs) exists. OTRs are located in the uterus, mammary glands, brain, kidneys, thymus, ovary and testes. VP will bind to both VPRs and OTRs, whereas OT will only bind to OTRs.
VPRs and OTRs are themselves members of a larger family of receptors called G-protein coupled membrane receptors. All the receptors of this family have a similar structure and location. G-protein coupled membrane receptors consist of a protein molecule that sits inside a cell membrane with parts of it that loop outside the cell membrane and parts of it that loop inside the cell itself. The part of the receptor that loops outside the cell forms four areas called extracellular domains. The part that loops inside the cell forms four areas called intracellular domains. The part of the receptor that stays inside the membrane forms seven distinct clumps called the seven helical (coiled) transmembrane domains. (Please look at the diagram of G-protein coupled receptor.)
The structures of the genes which create VPRs and OTRs are becoming increasingly understood. For example, the gene which creates the V2R has been extensively mapped due to the part it plays in causing a kidney disorder called nephrogenic diabetes insipidus (NDI). Researchers have found over 60 different mutations of the V2R gene which produce dysfunctional V2Rs, which, in turn, produces NDI. No mutations of the oxytocin or Vl receptors have been found.
OTRs and, to a much lesser extent, VPRs, do not maintain a constant number in the body: there may be many more of them at certain times due to certain conditions. For example, during gestation there are 100 times the OTRs in the uterus as there are under nongestational conditions. Estrogen is capable of signaling an increase in OTRs. VPRs have less dramatic swings in their number. There is some effect on V2R amounts in the kidney due to the presence of testosterone.