Endogenous cannabinoid

Endogenous cannabinoids Endogenous agonists of cannabinoid receptors... 

Di Marzo V, De Petrocellis L (2005) Plant, synthetic and endogenous cannabinoids in medicine. Annu Rev Med 57 553-574... 

The LVA ai subunits are blocked by moderate to low (10 pM) concentrations of nickel and bind the channel blocker mibefradil and kurotoxin. Both compounds are not specific LVA channel blockers because they block also Cavl. x and Cav2.x channels at about tenfold higher concentration. Interestingly, the endogenous cannabinoid anandamide binds to LVA channels and stabilises the inactivated state. This effect decreases T-type calcium current and neuronal firing activities. 

As outlined earlier, anandamide was the first among the endogenous cannabinoid receptor agonists to be identified. It exhibits higher binding affinity for the CBi receptor Ki — 89 nM) than for the CB2 receptor (il = 371 nM) [81]. Anandamide has typical cannabinoid activities including decreased spontaneous motor activity, immobility and production of hypothermia and analgesia [147, 148]. However, this action in vivo is of shorter duration than... 

Since the discovery of anandamide in 1992, a number of studies have examined its pharmacological properties. Although its roles are still elusive, a plethora of data supports the initial postulate that anandamide is the major endogenous cannabinoid ligand. As mentioned earlier, anandamide binds to CB1 from brain preparations and displaces various well-... 

All the foregoing pharmacological effects of anandamide, in conjunction with the well-documented existence of specific systems for its biosynthesis, catabolism, and cellular reuptake to be discussed shortly, suggest that anandamide is indeed the endogenous cannabinoid ligand. The other two less studied A -acylethanolamide endocannabinoids and also 2-AG may serve similar functions. The differential roles of each of these four endocannabinoids are still unclear. 

Aceto MD, Scates SM, Razdan RK, Martin BR. Anandamide, an endogenous cannabinoid has a very low physical dependence potential. J Pharmacol Exp Ther 1998 287 598-605. 

Cadas H, di Tomaso E, Piomelli D. Occurrence and biosynthesis of endogenous cannabinoid precursor, A-arachidonyl phosphatidylethanolamine, in rat brain. J Neurosci 1997 17 1226-1242. 

Cadas H, Gaillet S, Beltramo M, Venance L, Piomelli D. Biosynthesis of an endogenous cannabinoid precursor in neurons and its control by calcium and cAMP. J Neurosci 1996 16 3934-3942. 

Calignano A, LaRana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids. Nature 1998 394 277-281. 

Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 1999 2 358-363. 

Hillard CJ, Cambell WB. Biochemistry and pharmacology of arachidonyl-ethanolamide, a putative endogenous cannabinoid. J Lip Res 1997 38 2383-2398. 

Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 2001 29 717-727. 

Mackie K, Devane WA, Hille B. Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N-18 neuroblastoma cells. Mol Pharmacol 1993 44 498-503. 

Martin BR, Mechoulam R, Razdan RK. Discovery and characterization of endogenous cannabinoids. Life Sci 1999 65 573-595. 

Ohno-Shosaku T, Maejima T, Kano M. Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 2001 29 729-738. 

Piomelli D, Beltramo M, Giuffrida A, Stella N. Endogenous cannabinoid signaling. Neurobiol Dis 1998 5 462-473. 

Smith PB, Compton DR, Welch SP, Razdan RK, Mechoulam R, Martin BR, The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice. J Pharmacol Exp Ther 1994 270 219-227. 

Stella N, Schweitzer P, Piomelli D. A second endogenous cannabinoid that modulates long-term potentiation. Nature 1997 388 773-778. 

Wilson RI, Nicoll RA. Endogenous cannabinoids mediate retrograde signaling at hippocampal synapses. Nature 2001 410 588-592. 

Once THC is bound to presynaptic and postsynaptic receptor sites, a way to stop its action is required. Otherwise, stimulation could continue indefinitely and a perpetual high could be maintained from just a few puffs of marijuana. Research has shown that the endogenous cannabinoid anandamide is deactivated by being removed from receptors and transported into the cell, where it is broken down by an enzyme into nonactive components. This process is believed to be the same for THC. 

Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR and Lichtman AH (2001). Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proceedings of the National Academy of Science, 98, 9371-9376. 

Marijuana and hashish are derivatives of the cannabis sativa plant. Although cannabinoids have been used for centuries for recreational and therapeutic purposes, dramatic advances in cannabinoid neurobiology have occurred since 1990 [34-37]. This is attributable to the cloning of cannabinoid receptors and the discovery of endogenous cannabinoids, termed endocannabinoids. 

Gurwitz, D. and Kloog, Y., Do endogenous cannabinoids contribute to HIV-mediated immune failure , Mol. Med. Today, 4, 196, 1998. 

Several physiological roles of endocannabinoids have been identified, including memoiy, cognition, movement, and pain perception (Stella et al. 1997). Elucidation of the endocannabinoid systems is essential to the understanding of the effects of cannabis. There are both similarities and some pointed differences between the effects of exogenous and endogenous cannabinoids. 

Childers SR, Breivogel CS. (1998). Cannabis and endogenous cannabinoid systems. Drug Alcohol Dependence. 51(1-2) 173-87. 

Romero J, de Miguel R, Garcia-Palomero E, Fernandez-Ruiz JJ, Ramos JA. (1995). Time-course of the effects of anandamide, the putative endogenous cannabinoid receptor ligand, on extrapyramidal function. Brain Res. 694(1-2) 223-32. 

Huang SM, Strangman NM, Walker JM. 1999. Liquid chromatographic-mass spectrometric measurement of the endogenous cannabinoid 2-arachidonylglcerol in the spinal cord and peripheral nervous system. Zhongguo Yao Li Xue Bao 20 1098. 

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