Prostaglandins cortex

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

Both the medulla and the cortex of the kidney synthesize prostaglandins, the medulla substantially more than the cortex. COX-1 is expressed mainly in cortical and medullary collecting ducts and mesangial cells, arteriolar endothelium, and epithelial cells of Bowman s capsule. COX-2 is restricted to the renal medullary interstitial cells, the macula densa, and the cortical thick ascending limb. 

Exner HJ, Schlicker E (1995) Prostanoid receptors of the EP3 subtype mediate the inhibitory effect of prostaglandin E2 on noradrenaline release in the mouse brain cortex. Naunyn-Schmiedeberg s Arch Pharmacol 351 46-52. 

Fig. 4 Effect of various peptides and nonpeptides on the electrically (3 Hz) evoked tritium overflow from superfused mouse brain cortex slices preincubated with 3H-serotonin. The evoked overflow represents quasi-physiological exocytotic serotonin release. In all experiments, serotonin autoreceptors were blocked by metitepine. The figure shows that human neuropeptide Y concentration-dependently inhibited serotonin release and that this effect was mimicked by human neuropeptide Y (13-36) (NPYi3 36), which has a high affinity for Y2 but a very low affinity for Yi receptors. These results are compatible with the view that neuropeptide Y acts via Y2 receptors in the present model. For the sake of comparison, the figure also shows the inhibitory effects of another three agonists, acting via cannabinoid CBi, histamine H3 and prostaglandin EP3 receptors and used at concentrations causing the maximum or near-maximum effect at their respective receptors. Drug concentrations in pM. P < 0.05, P < 0.003, compared to the control (from Nakazi et al. 2000 and Nakazi 2001 redrawn).

Kearns, S.D. and Haag, M., The effect of omega-3 fatty acids on Ca-ATPase in rat cerebral cortex, Prostaglandins Leukot. Essent. Fatty Acid, 67, 303, 2002. 

Fig. 2. General scheme for transduction of ACTH signal from plasma membrane to mitochondria in the adrenal cortex. CHX, cycloheximide TG. triglyceride CE, cholesterol ester Lts, leukotrienes PGs, prostaglandins SCP2, sterol carrier protein PE, PC, PI, phosphatidyl ethanolamine, choline and inositol (from Ref. 25, with permission).

Synthesis of prostaglandins (PGE2 and PGF2 ) and their release into cerebral ventricular fluid have been reported to occur in mammalian central nervous system tissue. Levels of prostaglandins tend to range from 0.1 to 2.5 pg/g tissue. Their presence has been reported in cerebral cortex, cerebellum, and hippocampus, and levels can be enhanced in the presence of norepinephrine and other catecholamines. Thromboxane synthesis has also been reported to occur. The trace amounts of prostacyclin are probably the result of contamination of brain preparations with vascular elements. 

Several pharmacologically active substances are present in superfusates of the cerebral cortex, including acetylcholine, 5-hydroxytryptamine, substance P and the prostaglandins. Members of this latter family of hydroxy-unsaturated fatty acids are released from a great variety of tissues on nerve and hormone stimulation (Ramwell and Shaw 1970), and have been shown to possess a wide range of biological activity (Horton, 1969). 

The release of prostaglandins from the cerebral cortex of the anaesthetised cat was first reported by Ramwell and Shaw (1966). The level of release could be increased by stimulation of the contralateral forepaw and by administration of analeptics, suggesting that prostaglandin release might be connected with neuronal activity. 

Bradley, P. B., Samuels, G. M. R. and Shaw, J. E. (1969) Correlation of prostaglandin release from the cerebral cortex of cats with the electrocorticogram following stimulation of the reticular formation. Brit. J. Pharmacol., 37,151-157. 

Molenaar Could there be any release of prostaglandin from blood vessels in the cortex ... 

Kataoka, K., Ramwell, P. W. and Jessup, S. (1967) Prostaglandins Localisation in subcellular particles of rat cerebral cortex. Science, 157,1187-1189. 

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