Abstract
In order to understand the molecular basis of the elevated cerebral prostaglandin levels in the newborn, we compared the expression of the mRNAs and proteins of prostaglandin G/H synthases (PGHS), PGHS-1 and PGHS-2, in various regions of the brain and the microvasculature of newborn (1-2-day-old) and juvenile (4-7-week-old) pigs and also measured the relative contribution of PGHS-2 to cerebral prostaglandin synthesis both in vivo and in vitro by using a novel inhibitor of PGHS-2, NS-398. Ribonuclease protection assays using total RNA isolated from various regions of the porcine brain revealed that, unlike PGHS-1 mRNA, PGHS-2 mRNA was abundantly expressed in the cortex and the microvasculature of the newborn compared with those of the juvenile animal. PGHS-2 immunoreactive protein comprised the majority of total PGHS enzyme in neonatal cerebral microvasculature due to a 2-3-fold lower expression of immunoreactive PGHS-1 protein. Inhibition of PGHS-2 by NS-398 decreased the rate of prostaglandin synthesis by purified cerebral microvessels of the newborn by approximately 65% and of juvenile pigs by 30%. The decrease in brain tissue prostaglandin concentrations following intravenous administration of NS-398 was greater in newborn pigs (> or = 90%) than in the juvenile animals (< or = 30%). Furthermore, NS-398 substantially reduced the net in vivo cerebrovascular production of prostaglandins in newborn pigs. Taken together, these results indicate that PGHS-2 is the predominant form of prostaglandin G/H synthase in the newborn brain and cerebral microvasculature and the main contributor to the brain prostaglandin levels in the newborn animal.
Highlights
Prostaglandins act as modulators in several neurological [1, 2] and cerebral hemodynamic functions [3, 4]
NS-398 substantially reduced the net in vivo cerebrovascular production of prostaglandins in newborn pigs. These results indicate that prostaglandin G/H synthases (PGHS)-2 is the predominant form of prostaglandin G/H synthase in the newborn brain and cerebral microvasculature and the main contributor to the brain prostaglandin levels in the newborn animal
We examined the relative contribution of PGHS-2 to the cerebral production of prostaglandins both in vivo and in vitro by using a PGHS-2 inhibitor, NS-398
Summary
Prostaglandins act as modulators in several neurological [1, 2] and cerebral hemodynamic functions [3, 4]. Ribonuclease protection assays using total RNA isolated from various regions of the porcine brain revealed that, unlike PGHS-1 mRNA, PGHS-2 mRNA was abundantly expressed in the cortex and the microvasculature of the newborn compared with those of the juvenile animal.
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