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      Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats

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          Abstract

          Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

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          Most cited references23

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          Cyclooxygenases 1 and 2.

          Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.
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            Distinct functions of COX-1 and COX-2.

            The enzymes that convert arachidonic acid to prostaglandin H2 are named cyclooxygenase-1 (COX-1) and COX-2. The properties of COX-1 are different from those of COX-2. It was originally thought that the function of COX-1 was involved in physiological phenomena, whereas that of COX-2 was involved in various pathologies. However, studies with COX-2 knockout mouse suggest that COX-2 also plays important roles in development and homeostasis. This chapter focuses on the distinct functions of COX-1 and COX-2.
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              Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues.

              The rate-limiting step in the formation of prostanoids is the conversion of arachidonic acid to prostaglandin H2 by cyclooxygenase, also known as prostaglandin G/H synthase/cyclooxygenase. Two forms of cyclooxygenase have been characterized: a ubiquitously expressed form (COX-1) and a recently described second form (COX-2) inducible by various factors including mitogens, hormones, serum and cytokines. Here we quantitate by the reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of COX-1 and COX-2 mRNA in human tissues including lung, uterus, testis, brain, pancreas, kidney, liver, thymus, prostate, mammary gland, stomach and small intestine. All tissues examined contained both COX-1 and COX-2 mRNA and could be grouped according to the level of COX mRNA expression. The highest levels of COX mRNAs were detected in the prostate where approximately equal levels of COX-1 and COX-2 transcripts were present. In the lung high levels of COX-2 were observed whereas COX-1 mRNA levels were about 2-fold lower. An intermediate level of expression of both COX-1 and COX-2 mRNA was observed in the mammary gland, stomach, small intestine, and uterus. The lowest levels of COX-1 and COX-2 mRNA were observed in the testis, pancreas, kidney, liver, thymus, and brain.
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                Author and article information

                Journal
                Korean J Physiol Pharmacol
                Korean J. Physiol. Pharmacol
                KJPP
                The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
                The Korean Physiological Society and The Korean Society of Pharmacology
                1226-4512
                2093-3827
                July 2017
                26 June 2017
                : 21
                : 4
                : 407-413
                Affiliations
                Cardiovascular Pharmacology and Hyperbaric Experimental Medicine, Escuela Superior de Medicina, Instituto Politecnico Nacional, 11340 Mexico City, Mexico.
                Author notes
                Correspondence: Maria C. Castillo-Hernandez. castillohernandezmc@ 123456gmail.com , ccastillohe@ 123456yahoo.com.mx
                Article
                10.4196/kjpp.2017.21.4.407
                5507779
                b9872e51-6297-4971-b409-6f9172c34116
                Copyright © 2017 The Korean Physiological Society and The Korean Society of Pharmacology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 February 2017
                : 08 March 2017
                : 04 April 2017
                Funding
                Funded by: Escuela Superior de Medicina, IPN;
                Funded by: Comisión de Operación y Fomento de Actividades Académicas, Instituto Politécnico Nacional, CrossRef http://dx.doi.org/10.13039/501100007177;
                Categories
                Original Article

                aorta,cyclooxygenase,development,heart,phenylephrine
                aorta, cyclooxygenase, development, heart, phenylephrine

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