Purinoceptor agonists

Jacobson KA, van Rhee AM. Development of selective purinoceptor agonists and antagonists. In Jacobson KA, Jarvis MF, eds. Purinergic Approaches in Experimental Therapeutics. New York Wiley-Liss, 1997 101-128. 

Inscho EW, Cook AK,MuiV, Miller J Direct assessment of renal microvascular responses to P2-purinoceptor agonists. Am.J.Physiol 274 F718-F727,1998... 

More recently, studies have been performed to determine the responsiveness of rat juxtameduUary afferent arterioles to receptor-selective P2- purinoceptor agonists [246]. Experiments were performed in vitro using the blood perfused juxtameduUary nephron technique, combined with videomicroscopy. The presence of multiple P2 receptors on juxtameduUary afferent arterioles and the classification of these receptors as members of the P2X- and P2Y2 (P2U)-receptor subtypes was demonstrated. In another study, the relative contributions of adenosine A1 and A2a receptors to the responsiveness of the renal microvasculature to adenosine was investigated [247]. The presence of adenosine A1 and A2a receptors on afferent and efferent arterioles of juxtameduUary nephrons was demonstrated. Also, adenosine A2a receptor-mediated vasodilation partially buffered adenosine-induced vasoconstriction in both pre- and postglomerular segments of the renal microvasculature. 

Trezise, D.J., Michel, A.D., Grahames. C.B., Khakh, B.S., Surprenant, and Humphrey, P.P. (1995) The selective P2X purinoceptor agonist, beta,gamma-methylene-L-adenosine 5 -triphosphate, discriminates between smooth muscle and neuronal... 

Fuder H, Muth U (1993) ATP and endogenous agonists inhibit evoked [3H]-noradrenahne release in rat iris via Ai and P2Y-like purinoceptors. Naunyn-Schmiedeberg s Arch Pharmacol... 

Fuder H, Brink A, Meincke M et al (1992) Purinoceptor-mediated modulation by endogenous and exogenous agonists of stimulation-evoked [3H]-noradrenaline release on rat iris. Naunyn Schmiedeberg s Arch Pharmacol 345 417-23... 

ADENOSINE RECEPTOR AGONISTS act extra-cellularly at receptors variously known as adenosine receptors, PI purine receptors, PI receptors, P purinoceptors, or nucleoside receptors. Adenosine receptors have a wide range of mainly inhibitory actions in the body, including cardiac slowing, a fall in blood pressure, dilation of bloqd vessels, inhibition of platelet aggregation, inhibition of intestinal movements and actions within the central nervous system. 

IB-MECA is an adenosine derivative, active as a (PI purinoceptor) ADENOSINE RECEPTOR AGONIST selective at the As-subtypc. It is used as a tool in adenosine receptor studies. It is reported to show cerebral antiischaemic activity in an animal model also induces apoptosis in a human leukaemic cell line. 

PURINE P2 RECEPTOR AGONISTS (previously called Pa purinoceptors) are nucleotide-sensitive receptors that are dealt with under this heading whereas P purinoceptors, which are nucleoside-sensitive, may be found under another heading see adenosine receptors. P2 receptors can be activated extracelluiarly by nucleotides, including purines... 

P2X, receptors show an order of potency for the natural ligands ATP > ADP and the unnatural ligands a.P-methylene-ATP and ATP-y-S are useful investigational agonists, but desensitization is very evident. These receptors are found in a number of smooth muscle preparations including arterioles, vas deferens and the urinary bladder, where they cause depolarization and contraction. They are found only in neonate brains. The form of the receptor here seems to be a homopolymer formed of identical units. At these sites, the ejps (excitatory junction potentials) seen on sympathetic nerve stimulation are caused in response to ATP action at P2X purinoceptors when it is liberated - as a cotransmilter - from sympathetic varicosities. 

PURINE P2 RECEPTOR ANTAGONISTS P2 receptors (P2-purinoceptors) are quite distinct from PI receptors (see ADENOSINE RECEPTORS), with the former activated by nucleotides, typically ATP and the latter by nucleosides, typically adenosine see purine receptor agonists. As a result of coupling considerations and structural information derived from cloning and expression studies, the P2 purinoceptors are now divided into two main classes. 

To test the specificity of PPADS, we compared its blocking activity on P2-purinoceptor-mediated responses with its effects on responses mediated by a -adrenoceptors in rat vas deferens, histamine H]-receptors and muscarinic M3-receptors in guinea-pig ileum, adenosine A j-receptors and muscarinic M2-receptors in guinea-pig atria and adenosine A2-receptors and muscarinic Mj-receptors in rat duodenum. PPADS (100 pM) had no significant effect on either the potency or maximum responses to the respective agonists used in the various receptor preparations. These results demonstrate that the antagonistic effects of PPADS against purine-nucleotides at P2-purinoceptors are specific. 

Key Words CBi receptor agonists CBi receptor antagonists cannabidiol 6"-azido-2"-yne-cannabidiol abnoimal-cannabidiol P2X purinoceptors ai-adrenoceptors vanilloid (TRPVl) receptors SR141716A R-(-t)-WIN55212 CP55940 anandamide ATP phenylephrine. 

Nucleoside Triphosphates and Their Analogues. - A review has been given of the most useful methods for the synthesis of nucleoside triphosphates. 5 -Triphosphates of 8-(alkylthio)adenosines have been prepared as inhibitors of nucleoside triphosphate diphosphohydrolase, and the triphosphates 202 and that derived from 2,2 -anhydrouridine have been made as agonists for P2X2-purinoceptors, but they showed lesser potencies than the parent nucleosides. Derivatives of ATP, UTP and CTP have been prepared in which methyl ketone groups are attached via spacers to the base units, in order to permit interaction with fluorescent probes after enzymic incorporation into oligonucleotides. The triphosphate was assembed by Eckstein s procedure, in which a 2, 3 -0-iso-propylidene nucleoside is treated sequentially with salicyl phosphorochloridite, pyrophosphate and an oxidant. ... 

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