Prostanoid receptors: ontogeny and implications in vascular physiology

1 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G-1Y6; 2 Theratechnologies, St. Laurent, Quebec H4S-2A4; and 3 Departments of Pediatrics, Ophthalmology, and Pharmacology, Research Center of Hôpital Ste. Justine, Montreal, Quebec H3T-1C5, Canada; and 4 University of California, San Francisco, California 94143 Prostanoids exert significant effects on circulatory beds. They play a role in the response of the vasculature to adjustments in perfusion pressure and oxygen and carbon dioxide tension, and they mediate the actions of numerous factors. The role of prostanoids in governing circulation of the perinate is suggested to surpass that in the adult. Prostanoids are abundantly generated in the perinate. They have been implicated in autoregulation of blood flow as studied in brain and eyes. Prostaglandins are also dominant regulators of ductus arteriosus tone. The effects of these autacoids are mediated through specific G protein-coupled receptors. In addition to the pharmacological characterization of the prostanoid receptors, important advances in understanding the biology of these receptors have been made in the last decade. Their cloning and the development of animals with disrupted genes of these receptors have been very informative. The involvement of prostanoid receptors in the developing subject, especially on brain and ocular vasculature and on ductus arteriosus, has also begun to be investigated; the expression of these receptors changes with development. Some but not all of the ontogenic changes in these receptors are attributed to homologous regulation. Interestingly, in the process of elucidating their effects, functional perinuclear prostaglandin E 2 receptors have been uncovered. This article reviews prostanoid receptors and addresses implications on the developing subject with attention to vascular physiology. G protein-coupled receptors; brain vasculature; eye vasculature; ductus arteriosus; newborn