Patch clamp study on mechanism of adenosine-induced inhibitory effects in frog pituitary melanotrophs.
Our laboratory demonstrated that adenosine inhibits the activation of adenylyl cyclase and the secretion of the alpha-melanocyte-stimulating hormone (alpha-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 alpha-MSH. The results show that adenosine acting on A1 adenosine receptor subtype reduced the Ca2+ 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 (lk), 3) a diminution of the cellular excitability by an activation of the transient outward K+ current (lA), and 4) an inhibition of the L- and N-type Ca2+ currents, with a predominant action on the N-type component. Cell dialysis with GTP gamma S rendered irreversible the effects of adenosine on the K+ conductances and Ca2+ 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 Ca2+ 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.
Mei
Y A
YA
Department of Physiology, Shanghai Second Medical University, China.
Vaudry
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Cazin
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D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism*
D015220:Calcium Channels; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D000521:alpha-MSH; D000241:Adenosine