Arachidonic acid derivatives

Only little information is available as to the role of arachidonic acid derivatives in VIP-stimulated PRL release. As in the case of TRH, agents that inhibit arachidonic acid generation blunt the PRL response to VIP [122]. 

In in vitro anterior pituitary assay systems prostaglandins do not stimulate basal LH release and cyclooxygenase inhibitors do not inhibit LHRH-stimulated LH release 

The potentiation of the ACTH response to CRF by vasopressin also seems to be based on the arachidonic acid derivative system, as vasopressin-stimulated ACTH secretion is inhibited by lipoxygenase inhibitors [141]. 

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A different type of endocannabinoid that is also an arachidonic acid derivative was first isolated from canine gut and identified as 2-arachidonyl glycerol (2-AG) (Fig. 3) (Mechoulam, 1995a). 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

The asymmetric Horner-Wadsworth-Emmons (HWE) reaction of l,3-dioxan-5-ones with phosphonate 184 and a chiral diamine was reported. With the /i r/-butyl-substituted l,3-dioxan-5-one, the product possesses a chiral axis. It was obtained in good yield and with 80% ee (Scheme 53) <2002TL281>. The HWE reaction with similar heterocyclic substrates was used to provide conformationally restricted arachidonic acid derivatives <1999TA139>. 

Cyclooxygenase (COX), one of the two activities of prostaglandin endoperoxide synthase (PGHS), is the key enzyme in the conversion of arachidonic acid derived from lipids of the cell membrane to prostaglandins and other eicosanoids (Fig. 3). 

The precise mechanism of post-traumatic vasogenic edema is unknown, but Chan and colleagues [51] have provided data suggesting an important role for an arachidonic-acid-derived oxygen-radical-mediated process. In initial in vitro experiments, it has been discovered that when rat-brain cortical slices are... 

Prostaglandins, thromboxanes and leucotrienes are eicosanoids deriving from oxidation of arachidonic acid. Arachidonic acid (deriving from PLA2 action on phospholipids) is cyclized by constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2) to yield... 

Laffi G (1997) Arachidonic acid derivatives and renal function in liver cirrhosis. Semin Nephrol 17 530-548. 

As a general rule, ylides with allylic or benzylic functionality do not proceed with a high degree of stereoselectivity. There have been recent examples of arachidonic acid derivatives in which the coupling of an allylic phosphonium salt with an unsaturated aldehyde resulted in (Z)-selective alkenation. As in the case of nonstabilized ylides, replacing aromatic phosphorus substituents with allylic (113 equation 25) or alkyl (115 equation 26) groups dramaticaUy increases the production of the (, -al-kene. ... 

Pho.sphoinosiiides serve as storage forms for secondary messengers. Phosphoinositidc.s compose only a minor fraction (2-8 f) of the lipids in cell membranes, yet they can be converted to at least three intracellular messenger molecules arachidonic acid, inositol 1.4,5-ua.sphosphale (IP i). and 1.2-diacylglyeerol (DAG). The functions of arachidonic acid derivatives are discus.sed in Chapter 24. IP releases intracellular calcium, and DAG is an essential cofuctor in the activation of protein kina.se C." ... 

Arachidonic acid, derived from membrane phospholipids, is the precursor for synthesis of the leukotrienes. 

Endogenous ligands for the cannabinoid receptor have not yet been identified. Arachidonylethanolamide, a new arachidonic acid derivative named anandamide, was isolated from porcine brain. Its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. It inhibits the specific binding of a labelled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands, and produces a concentration-dependent inhibition of the electrically-evoked twitch response of the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. Similar compounds were synthesized and their pharmacological properties were investigated. 

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