Characterization of 5'-N-ethylcarboxamido[3H]adenosine binding to pig aorta smooth muscle membranes

Biochem Pharmacol. 1987 Nov 1;36(21):3621-7. doi: 10.1016/0006-2952(87)90011-6.

Abstract

Binding of 5'-N-ethylcarboxamido[3H]adenosine ([3H]NECA) to pig aorta smooth muscle membranes was rapid, reversible and dependent on protein concentration and temperature. Due to a rapid rate of dissociation binding was highest at 0 degree. Binding was saturable and Scatchard analysis revealed two different binding sites for [3H]NECA with KD values of 0.29 and 4.64 microM and Bmax values of 9.3 and 35.5 pmol mg-1. GTP, Mg2+, Mn2+ and Ca2+ did not affect the binding. (-)[N6]-[3H]phenylisopropyladenosine ([3H]PIA) bound to pig aorta smooth muscle membranes with very low affinity and non-specific binding was high (50%), in contrast to that for [3H]NECA (less than 10%). In competition studies, NECA and 5'-N-methylcarboxamidoadenosine were the most potent displacers of [3H]NECA followed by adenosine, 2-chloroadenosine and 2',5'-dideoxyadenosine. (-)PIA and N6-cyclohexyladenosine, potent A1 receptor agonists, did not compete for [3H]NECA binding sites. The xanthines, 3-isobutyl-l-methylxanthine and theophylline, inhibited [3H]NECA binding, but, in contrast, 8-phenyltheophylline, a potent adenosine antagonist in other systems, did not compete for binding sites. No effect of NECA nor (-)PIA on adenylate cyclase activity could be demonstrated, whereas forskolin increased activity 17-fold. Similarly, the same adenosine analogues incubated with intact slices of rat aorta smooth muscle failed to elevate tissue cAMP levels, although forskolin elicited a 37-fold increase. These results demonstrate low affinity [3H]NECA binding sites in pig aorta smooth muscle with properties similar to those described in lung and platelet membranes but which differ from characteristic A2-receptors in certain features.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Adenosine-5'-(N-ethylcarboxamide)
  • Adenylyl Cyclases / analysis
  • Animals
  • Aorta / metabolism
  • Binding Sites
  • Cyclic AMP / analysis
  • In Vitro Techniques
  • Male
  • Muscle, Smooth, Vascular / metabolism*
  • Phenylisopropyladenosine / metabolism
  • Receptors, Purinergic / analysis
  • Swine

Substances

  • Receptors, Purinergic
  • Phenylisopropyladenosine
  • Adenosine-5'-(N-ethylcarboxamide)
  • Cyclic AMP
  • Adenylyl Cyclases
  • Adenosine