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Adenosine Inhibits L‐ and N‐Type Calcium Channels in Pituitary Melanotrophs. Evidence for the Involvement of a G Protein in Calcium Channel Gating
Author(s) -
Mei Yan Ai,
Foll Frank,
Vaudry Hubert,
Cazin Lionel
Publication year - 1996
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.1996.tb00827.x
Subject(s) - medicine , adenosine , endocrinology , cgs 21680 , chemistry , adenosine receptor , agonist , adenosine a1 receptor , patch clamp , calcium channel , calcium , receptor , biology
It has been previously demonstrated that activation of A 1 adenosine receptors in frog melanotrophs causes inhibition of spontaneous action potential discharges and alpha‐melanocyte‐stimulating hormone secretion. In the present study, we have investigated the effect of adenosine on high‐voltage‐activated (HVA) calcium currents in cultured melanotrophs, using the whole‐cell variant of the patch‐clamp technique with barium as a charge carrier. Adenosine and the specific A 1 adenosine receptor agonist R‐PIA (50 μM each) produced a decrease of the amplitude of the barium current, while the selective A 2 adenosine receptor agonist CGS 21680 did not affect the current. The inhibitory effect of R‐PIA was observed throughout the activation range of the current, with stronger responses at more positive potentials. R‐PIA inhibited both the L‐ and N‐type components of the current, the effect on the N‐component being two‐fold higher than on the L‐component. The inhibitory effect of R‐PIA was rendered irreversible by addition of GTPyS (100 μM) to the intracellular solution. Pre‐treatment of the cells with pertussis toxin (1 μg/ml; 12 h) totally abolished the effect of R‐PIA on the HVA calcium channels. Conversely, addition of a high concentration of cAMP (100 μM) together with the phosphodiesterase inhibitor IBMX (100 μM) to the intracellular solution did not modify the effect of R‐PIA on the current. It is concluded that, in frog melanotrophs, adenosine induces inhibition of L‐ and N‐calcium currents and that this effect is mediated by a pertussis toxin‐sensitive G protein. Our data also indicate that the inhibitory effect of adenosine on the calcium currents is not mediated by inhibition of adenylyl cyclase.