Adenosine A1 receptor-induced inhibition of Ca2+ transients linked to action potentials in clonal pituitary cells.
Adenosine is a potent paracrine/autocrine feedback inhibitor of cell activation in a variety of tissues. Adenosine action was studied in pituitary cells, in which spontaneous electrical activity causes characteristic oscillations of the cytosolic free Ca2+ concentration, [Ca2+]i. Cells of the GH3B6 rat pituitary tumor line were studied by microspectrofluorimetry using the Ca2+ probes indo-1 and fura-2, in part in combination with electrophysiological tight seal whole cell recordings, obtained with the novel approach of patch perforation. It was demonstrated that adenosine receptor activation by N6-(R-phenyl-isopropyl)-adenosine (PIA) caused a block of electrical activity and abolished the ensuing alterations in [Ca2+]i. PIA mimicked the inhibitory action of somatostatin. Adenosine effects are mediated by A1 receptors in these cells and are antagonized by IBMX, an adenosine receptor blocker. PIA also suppressed action potentials that were elicited by the activation of protein kinase C with the phorbol ester PMA, or during the second phase of TRH action. In contrast, no interference was notable on TRH-induced intracellular Ca2+ mobilization. In addition to the abolition of Ca2+ transients, PIA lowers basal [Ca2+]i in some cells. It is proposed that in addition to the inhibition of adenylate cyclase, A1 receptor action on [Ca2+]i is an important element in the control of excitable pituitary cells.
Laboratoire de Neurophysiologie, URA CNRS 1200, Université de Bordeaux II, France.
P
P
Mollard
N
N
Guérineau
C
C
Chiavaroli
W
W
Schlegel
D M
DM
Cooper
D000200:Action Potentials / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D007211:Indoles; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D011983:Receptors, Purinergic / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology
D007211:Indoles; D011983:Receptors, Purinergic; C059587:Indo-1 pentaacetoxymethyl ester; D010660:Phenylisopropyladenosine; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D011493:Protein Kinase C; D000241:Adenosine; D002118:Calcium