In vivo pertussis toxin treatment attenuates some, but not all, adenosine A1 effects in slices of the rat hippocampus.
In order to examine the involvement of G-proteins in mediating the different effects of adenosine A1-receptor stimulation in rat hippocampus we injected pertussis toxin (PTX) intraventricularly close to the hippocampus and examined its effect in slices 48-60 h later. The in vivo PTX treatment caused a partial (50 +/- 5%) inhibition of the [32P]ADP ribosylation produced by PTX added together with [32P]NAD in vitro. Such PTX treatment eliminated the electrophysiologically determined gamma-amino-n-butyric acid (GABA)B receptor response in the hippocampal CA1 region, but GABAA effects were unaffected. The adenosine (50 microM)-mediated hyperpolarization and decrease in input resistance as well as the adenosine-mediated inhibition of low calcium-induced bursting in pyramidal CA1 neurons were virtually abolished. The same was true for the decrease in [3H]cyclic AMP accumulation that is produced by the adenosine analogue R-N6-phenylisopropyl adenosine (R-PIA) in forskolin-treated hippocampal slices. As far as modulation of transmitter release was concerned, the R-PIA (1 microM)-induced inhibition of release of both [3H]noradrenaline (NA) and [3H]acetylcholine (ACh) evoked by field stimulation in hippocampal slices was affected hardly or not at all by pertussis toxin treatment. The inhibitory effect of adenosine on field excitatory postsynaptic potential (EPSP)s evoked in the CA1 region was unaltered by PTX pretreatment. The present results show that in vivo pertussis toxin treatment can inhibit some but not all A1-adenosine-receptor effects. This strongly suggests that closely similar A1 receptors might be coupled to G-proteins that differ in their sensitivity to PTX treatment.
Fredholm
B B
BB
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Proctor
W
W
Van der Ploeg
I
I
Dunwiddie
T V
TV
D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D037342:Pertussis Toxin; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D010761:Phosphorus Radioisotopes; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D015016:Yohimbine; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000241:Adenosine; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine