On the high affinity of 8-cyclohexylcaffeine for the presynaptic inhibitory adenosine receptor present in rat motor nerve terminals

• Type: Article in International Scientific Journal
• Date: 1997

Authors

Lobo, MGB (Author) ICBAS; Oliveira, DG (Author) Other; Sebastiao, AM (Author) Other; Ribeiro, JA (Author) Other

Journal

Title: PHARMACOLOGY & TOXICOLOGY

Vol. 80

Pages: 295-300

ISSN: 0901-9928

Publisher: Blackwell

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-001-BCF

DOI: 10.1111/j.1600-0773.1997.tb01977.x

Abstract (EN): Rat neuromuscular junction was used to study the characteristics of presynaptic A(1) adenosine receptors. We investigated the ability of the 8-substituted caffeine, 8-cyclohexylcaffeine (CHC), as well as of 1,3,8-substituted xanthines, 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) and 8-p-sulfophenyl-1-isoamyl-3-isobutylxanthine (SPIIBX) to antagonize the inhibitory effect of 2-chloroadenosine on the amplitude of nerve-evoked twitches of the rat phrenic-hemidiaphragm, and we compared the affinity of these xanthines with that of 1,3-dipropyl-8-cyclopenthylxanthine (DPCPX). CHC, DPSPX and SPIIBX in a near parallel manner shifted to the right the log concentration-response curve for the inhibitory effect of 2-chloroadenosine on nerve-evoked twitch amplitude. Linear Schild plots with slopes near to unity were obtained for all these xanthines. The order of potency of the xanthines was DPCPX (K-i=0.53 nM) >DPSPX (38 nM) approximate to CHC (41 nM) >SPIIBX (404 nM). The affinities of DPSPX and SPIIBX for the A(1) receptor at the rat neuromuscular junction are in agreement with the affinities described for A(1) receptors at brain membranes. The now reported affinity of CHC for the presynaptic A(1) receptor is 683 times higher than that obtained in binding studies in rat brain membranes, and is only 49 times higher than that obtained in functional assays (adenylate cyclase activity) in non-neuronal preparations (rat fat cells).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6