Two distinct adenosine-sensitive sites on adenylate cyclase.

The effects of adenosine, adenosine analogues (N6-cyclohexyladenosine (CHA), L-N6-phenylisopropyladenosine (L-PIA), D-N6-phenylisopropyladenosine (D-PIA), N6-methyladenosine and 2-chloroadenosine), adenine, inosine, hypoxanthine, cyclic AMP and its analogue the dibutyryl cyclic AMP (db cyclic AMP), and methylxanthines (theophylline, caffeine and isobutylmethylxanthine (Ibmx) on compound action potentials were investigated in de-sheathed sciatic nerve preparations of the frog. 2 Adenosine and its analogues enhanced, in a concentration-dependent manner, the inhibitory action of tetrodotoxin (TTX) on nerve conduction. The order of potencies was: CHA > D-PIA > L-PIA> N6-methyladenosine > 2-chloroadenosine > adenosine. 3 The adenosine metabolites, inosine and hypoxanthine, were inactive on TTX-induced axonal blockade. Adenine enhanced the inhibitory action of TTX on nerve conduction, but was less effective than adenosine. 4 db Cyclic AMP, but not cyclic AMP, mimicked the inhibitory effect of adenosine on nerve conduction. 5 Methylxanthines did not antagonize the effect of adenosine on TTX-induced axonal block and in high concentrations also mimicked the effect of adenosine on nerve conduction. 6 The possibility of adenosine acting on TTX-induced axonal block through an adenosine receptor positively coupled to adenylate cyclase is discussed.

Section: Discussionmentioning

confidence: 99%

Enhancement of tetrodotoxin‐induced axonal blockade by adenosine, adenosine analogues, dibutyryl cyclic AMP and methylxanthines in the frog sciatic nerve

Ribeiro

Sebastião

1984

“…Adenosine, acting at cell surface A2-purinoceptors, activates adenylate cyclase to increase intracellular cyclic AMP (Londos & Wolff, 1977). In rat mast cells and human basophils, this is observed as an elevation and prolongation of the cyclic AMP response to immunological activation (Holgate et al, 1980;Hughes et al, 1983).…”

mentioning

confidence: 99%

Adenosine potentiates immunological histamine release from rat mast cells by a novel cyclic AMP‐independent cell‐surface action

Church

Hughes

1985

Adenosine enhanced histamine release and prolonged the adenosine 3': '-cyclic monophosphate (cyclic AMP) response in purified rat peritoneal mast cells following immunological challenge. The effect on the cyclic AMP response, which was blocked by 8-phenyltheophylline, probably results from an interaction with A2-purinoceptors. Enhancement of histamine release showed different characteristics. It was not inhibited by dipyridamole or hexobendine, thereby indicating an action at the cell surface. However, the relative potencies of adenosine analogues and nucleotides, together with the observation that this effect was not antagonized by 8-phenyltheophylline or theophylline, suggest that it is not mediated by a previously recognised purinoceptor. Thus, enhancement of histamine release may represent a novel cell surface action of adenosine which is independent of its effects on adenylate cyclase.

“…By using adenosine and its derivatives, Londos & Wolff (1977) (Van Calker et al, 1979;Londos et al, 1980). By interacting with one of these two receptor subtypes, adenosine can initiate a transmembrane signal to either inhibit (A1) or stimulate (A2) the AC activity.…”

Section: Discussionmentioning

confidence: 99%

Decreased arterial responsiveness to multiple cyclic AMP‐generating receptor agonists in spontaneously hypertensive rats

Masuzawa¹,

Matsuda²,

Asano³

1989

4 The relaxant responses due to activation of A2-adenosine. H2-histamine and Dj-dopamine receptors were significantly decreased in the SHR arteries. 5 Nitroprusside and nifedipine, agents which are independent of the Gs * AC system, produced similar arterial relaxations in the WKY and SHR. 6 These results support the hypothesis that a reduced function of Gs in the SHR is responsible for the decreased arterial responsiveness to a variety of receptor agonists whose mechanism of action involves AC activation.