A₁ adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea‐pig cerebral cortex

Abstract

<PD 155,199 (640). 9 In summary, we observe a good correlation between antagonist affinity at A1 receptors defined by radioligand binding, inhibition of cyclic AMP generation or augmentation of histamine-evoked phosphoinositide turnover in guinea-pig cerebral cortex.

Adenosine induces cyclic‐AMP formation and inhibits endothelin‐1 production/secretion in guinea‐pig tracheal epithelial cells through A2B adenosine receptors

“…In contrast, our results suggested that the stimulatory effect of CPA at the concentration of 1×10 −6 M was probably due to the activation of A 2B ‐adenosine receptor. Activation of cyclic AMP generation by A 1 ‐adenosine receptor agonists was also reported in guinea‐pig cerebral cortex where high concentrations of CPA, 2‐chloro‐ N 6 ‐cyclopentyladenosine (CCPA) and R ‐ N 6 ‐phenylisopropyladenosine (R‐PIA) stimulated the cyclic AMP generation presumably through the A 2B ‐adenosine receptor (Alexander et al ., 1994a). However, since potent and selective A 2B ‐adenosine receptor antagonists are not available, it was not possible to assess unequivocally that these effects are mediated by this receptor.…”

“…Comparable results were observed with the two other non selective adenosine receptor agonists, adenosine and 2CADO. The pD 2 values of these two agonists were shown to be 4.19 and 4.41 on HEK 293 endogenously expressing the A 2B ‐adenosine receptor (Cooper et al ., 1997), 5.69 and 5.27 in CHO cells expressing the A 2B ‐adenosine receptor cloned from human brain (Alexander et al ., 1996), 3.99 and 4.35 in guinea‐pig cerebral cortex (Alexander et al ., 1994a), 4.88 and 5.22 on guinea‐pig cerebellum (Hernandez et al ., 1993). In many experiments reported on A 2B ‐adenosine receptors, the selective A 2A agonist, CGS21680, was inactive (Casadó et al ., 1992; Hernandez et al ., 1993; Peakman & Hill, 1994; Feoktistov et al ., 1994; Brackett & Daly, 1994; Alexander et al ., 1994b, 1996; Strohme et al ., 1995; Feoktistov & Biaggioni, 1995; Fiebich et al ., 1996; Dubey et al ., 1996; Cooper et al ., 1997).…”

“…The results presented herein also suggested that the A 1 ‐adenosine receptor was not present on tracheal epithelial cells since no inhibitory effect on cyclic AMP was produced by CPA at concentrations that are reported to stimulate this receptor (Jacobson et al ., 1992; Alexander et al ., 1994a). Inhibition of forskolin‐induced cyclic AMP generation was reversed by CPA at concentrations of 1×10 −8 M , 1×10 −7 and 1×10 −6 M in guinea‐pig cerebral cortex and rat primary astrocytes (Peakman & Hill, 1994; Alexander et al ., 1994a). In contrast, our results suggested that the stimulatory effect of CPA at the concentration of 1×10 −6 M was probably due to the activation of A 2B ‐adenosine receptor.…”

Adenosine receptor‐mediated relaxation of guinea‐pig precontracted, isolated trachea

“…Thus, Al receptors are generally linked to inhibition of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) generation (Alexander et al, 1994a;Fredholm et al, 1994), while A2 receptors stimulate the production of cyclic AMP (Alexander et al, 1994b;Fredholm et al, 1994). In recent years, however, the subclassification of adenosine receptors has become more complex, with the acceptance of A3 receptors (Fredholm et al, 1994;Linden, 1994) and subtypes of A2 receptors (Fredholm et al, 1994).…”

Depolarizing and calcium-mobilizing stimuli fail to enhance synthesis and release of endocannabinoids from rat brain cerebral cortex slices

“…Activity was calculated as pmoles product/min/mg protein. We have previously determined that 25 μL gravity‐packed slices is approximately equivalent to 1 mg protein (Alexander et al. 1994).…”