In vivo behavioral assessment of central nervous system purinergic receptors. 1981

G G Yarbrough, and J C McGuffin-Clineschmidt

Administered intracisternally, adenosine (ADO), 2-chloroadenosine (CADO), adenosine-5'-cyclopropylcarboxamide (ACC) and adenosine-5'-ethylcarboxamide (AEC) caused dose-related increases in hot plate reaction times in mice. The rank order of potency was AEC=ACC greater than CADO greater than ADO and ACC exerted demonstrable effects with doses as low as 10 ng/mouse. ADO itself was more potent than AMP, ADP, ATP and several other related compounds of interest. Theophylline, caffeine and 8-phenyltheophylline antagonized the antinocisponsive effect of CADO or ACC. Papaverine (an adenosine uptake blocker) and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA: an adenosine deaminase inhibitor) potentiated the effect of ADO. EHNA did not potentiate the action of CADO in this procedure. The antinocisponsive effect of CADO was not antagonized by a host of neurally active agents including naloxone, clonidine and RO 20-1724. Time course studies indicated that the antinocisponsive effect of ADO was transient with the peak effect occurring 5 min after injection and disappearing by 60 min, whereas the effect of CADO persisted for at least 90 min. Intracisternally administered CADO also caused a pronounced hypothermia, loss of muscle tone and was active in the mouse writhing test. Taken together, these data demonstrate that purine exert potent in vivo behavioral effects and are consonant with the existence of a central purinergic P1-receptor which is amenable to selective pharmacological manipulation.

UI MeSH Term Description Entries
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D011930 Reaction Time The time from the onset of a stimulus until a response is observed. Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D011955 Receptors, Drug Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified. Drug Receptors,Drug Receptor,Receptor, Drug
D011983 Receptors, Purinergic Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP. Methyladenine Receptors,Purine Receptors,Purinergic Receptor,Purinergic Receptors,Purinoceptors,Purine Receptor,Purinoceptor,Receptors, Methyladenine,Receptors, Purine,Receptor, Purine,Receptor, Purinergic
D002490 Central Nervous System The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005260 Female Females
D006358 Hot Temperature Presence of warmth or heat or a temperature notably higher than an accustomed norm. Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D000700 Analgesics Compounds capable of relieving pain without the loss of CONSCIOUSNESS. Analgesic,Anodynes,Antinociceptive Agents,Analgesic Agents,Analgesic Drugs,Agents, Analgesic,Agents, Antinociceptive,Drugs, Analgesic

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