Adenosine A1 agonists and the Ca2+ channel agonist ...
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| Title | Adenosine A1 agonists and the Ca2+ channel agonist bay K 8644 produce a synergistic stimulation of the GTPase activity of Go in rat frontal cortical membranes |
| Author(s) | M. Sweeney-Nixon, A. Dolphin |
| Journal | Journal of Neurochemistry |
| Date | 1995 |
| Volume | 64 |
| Issue | 5 |
| Start page | 2034 |
| End page | 2042 |
| Abstract | The identity and role of G proteins in coupling adenosine receptors to effectors have been studied to a limited degree. We have identified the G proteins whose GTPase activity is stimulated by adenosine receptor agonists in neuronal membranes. (R)-Phenylisopropyladenosine, 2-chloroadenosine, and N-ethylcarboxamideadenosine produced a concentration-dependent stimulation of GTPase. At 10(-5) M, the increase above basal GTPase in frontal cortex was 25 +/- 4, 20 +/- 3, and 8 +/- 1%, respectively, and in the cerebellum 55 +/- 2, 41 +/- 4, and 22 +/- 2%, respectively. The effects of (R)-phenylisopropyladenosine and 2-chloroadenosine were inhibited by (1) A1 antagonists (76-96% reduction), (2) pretreatment with pertussis toxin (90-100% reduction), and (3) antibodies raised against the alpha-subunit of Gi and G(o) (55-57% reduction by each), suggesting that A1 receptors interact equally with Gi and G(o). (R)-Phenylisopropyladenosine increased the binding of a nonhydrolyzable analogue of GTP to membranes in a pertussis toxin-sensitive manner, indicative of activation of Gi or G(o). Previously, (+/-)-Bay K 8644 enhanced GTP hydrolysis by G(o) but not Gi. Now we report a profound synergistic stimulation of GTPase in the presence of (R)-phenylisopropyladenosine and (+/-)-Bay K 8644 (10(-7) to 10(-5) M). (+/-)-Bay K 8644 had no effect on nucleotide exchange and, thus, cannot activate G(o). It appears that a positive cooperative stimulation of G(o) occurs when it is first activated by A1 receptors and subsequently interacts with the L-type Ca2+ channel. |
| ISSN | 0022-3042 |
| Use/Reproduction | Contact Author |
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