Adenosine interaction with adenylate cyclase in rat posterior pituitary

Abstract

An adenosine-sensitive adenylate cyclase has been demonstrated in rat posterior pituitary in the present studies. N-Ethylcarboxamide adenosine (NECA), 2-chloroadenosine (2-Cl-Ado) and l- N 6-phenylisopropyladenosine (PIA) all stimulated adenylate cyclase in a concentration-dependent manner, with an apparent K a between 0.5 and 1 μM. NECA was most effective and stimulated adenylate cyclase by about 100%, whereas 2-Cl-Ado and PIA stimulated the enzyme activity by about 60%. The activation of adenylate cyclase by NECA was dependent on the concentrations of metal ions such as Mg 2+ or Mn 2+. The stimulatory effect of NECA on adenylate cyclase was completely blocked by 3-isobutyl-l-methylxanthine (IBMX) and 8-phenyltheophylline. Adenosine showed a biphasic effect on adenylate cyclase: stimulation at lower concentrations and inhibition at higher concentrations, whereas 2′-deoxyadenosine and 2′5′-dideoxyadenosine inhibited adenylate cyclase in a concentration-dependent manner. In addition, dopamine, isoproterenol and forskolin also stimulated adenylate cyclase to various degrees and the stimulatory effect of isoproterenol and forskolin was found to be additive with the stimulation exerted by NECA. These data indicate the presence of adenosine stimulatory receptors Ra/A 2 in posterior pituitary which are coupled to adenylate cyclase. It is possible that adenosine may act as one of the important regulators to regulate and/or modulate the release of posterior pituitary hormones