title: The antihypertensive effect of 2-alkynyladenosines and their selective affinity for adenosine A2 receptors.
abstract: We examined the affinity for adenosine receptors and the antihypertensive effects of 2-alkynyladenosines, especially 2-hexynyladenosine (2-H-Ado) and 2-octynyladenosine (2-O-Ado). The order of decreasing affinity of 2-H-Ado, 2-O-Ado, and other agonists tested for A1 receptors was N6-cyclopentyladenosine (CPA) greater than N6-cyclohexyladenosine (CHA) greater than N6-R-phenylisopropyladenosine (R-PIA) greater than 2-chloroadenosine (CADO) = 5'-N-ethylcarboxamideadenosine (NECA) greater than N6-S-phenylisopropyladenosine (S-PIA) greater than 2-H-Ado greater than 2-O-Ado greater than 2-phenylaminoadenosine (CV-1808), and that for A2 receptors was 2-H-Ado greater than 2-O-Ado = NECA greater than CADO greater than CV-1808 greater than R-PIA greater than CPA greater than CHA greater than S-PIA. The Ki values of 2-H-Ado and 2-O-Ado for [3H] NECA binding to A2 receptors were 4.1 and 12.1 nM, respectively, and those for [3H]CHA binding to A1 receptors were 146 and 211 nM, respectively: the affinity of 2-H-Ado and 2-O-Ado for A2 receptors was about 36- and 17-fold higher than their affinity for A1 receptors. Injection of 2-H-Ado and 2-O-Ado (0.03-100 micrograms/kg) decreased the blood pressure of anaesthetized spontaneously hypertensive rats (SHR). A slight decrease in heart rate was observed after i.v. injection of 100 micrograms/kg 2-H-Ado and 2-O-Ado. A potent and long-lasting antihypertensive effect was also observed after oral administration of 2-H-Ado and 2-O-Ado to conscious SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Research and Development Division, Yamasa Shoyu Co., Ltd., Choshi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Abiru
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Kogi
authors.forename: K
authors.initials: K
authors.lastname: Aihara
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000480:Alkynes / Q000378:metabolism / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002319:Cardiovascular System / Q000187:drug effects; D003243:Consciousness; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011983:Receptors, Purinergic / Q000378:metabolism*; D014316:Tritium; D014665:Vasodilator Agents / Q000378:metabolism
chemical_list: D000480:Alkynes; D000959:Antihypertensive Agents; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D014316:Tritium; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; C070493:2-hexynyladenosine; C070494:YT 146; D000241:Adenosine