Our laboratory demonstrated that adenosine inhibits the
activation of adenylyl cyclase and the
secretion of the α melanocyte
stimulating hormone (α MSH) from the intermediate lobe of the frog pituitary. This paper showed the bioelectric effects induced by adenosine, the ionic conductances modulated by adenosine, and the possible involvement of intracellular messengers, indicated the mechanism by which adenosine controls the
secretion of α MSH . The results show that adenosine acting on A 1 adenosine receptor subtype reduced the Ca 2+ influx necessary for the secretion, through 4 distinct mechanisms: 1) a hyperpolarization resulting from the
activation of a voltage insensitive K + conductance, 2) a reduction of the duration of spontaneous action potentials due to an increase of the outward delayed rectifyer K + current (I K), 3) a diminution of the cellular excitability by an activation of the transient outward K + current (I A), and 4) an inhibition of the L and N type Ca 2+ currents, with a predominant action on the N type component. Cell dialysis with GTPγS rendered irreversible the effects of adenosine on the K + conductances and Ca 2+ channels, whereas PTX pretreatment totally abolished the response to adenosine, suggesting all bioelectric effects of adenosine were mediated by pertussis toxin sensitive G proteins. Whether the implicated G proteins regulate the K + and Ca 2+ channels by tight coupling or via a second messenger system remains to be solved. With our results, the involvement of adenylyl cyclase can be excluded because addition of cAMP and IBMX, an inhibitor of phosphodiesterases, in the intracellular solution, or application of dibutyryl cAMP in the extracellular solution did not modify the adenosine induced responses.