Terminal serotonin autoreceptor function in the rat hippocampus is not modified by pertussis and cholera toxins.
The possibility that the terminal serotonin (5-HT) autoreceptor in the rat hippocampus is coupled to Gi, Go or Gs regulatory proteins was investigated using the electrically evoked overflow of [3H]5-HT from preloaded slices. Pertussis toxin, which inactivates Gi/o or cholera toxin, which stimulates Gs, was injected directly in the hippocampus 3 to 11 days prior to the experiments. Hippocampus slices were prepared, loaded with [3H]5-HT, superfused continuously, and stimulated electrically 72 min (S1) and 116 min (S2) after the beginning of superfusion. In the absence of any drug, the evoked overflow of [3H]5-HT in S1 was not altered by either toxin. The enhancing effect of the 5-HT reuptake blocker paroxetine (1 mumol/l) on the evoked [3H]5-HT overflow was also unaltered by these toxins. 5-Carboxyamidotryptamine, a 5-HT autoreceptor agonist, inhibited in a concentration-dependent manner the stimulation-evoked release of [3H]5-HT. The concentration-effect curve (0.001-0.1 mumol/l) for this drug was not altered by pretreatment with either pertussis or cholera toxin. Similarly, the effect of another 5-HT autoreceptor agonist, 5-methoxytryptamine (0.1 and 1 mumol/l), was not altered in the pretreated rats. In addition, the reduction of [3H]5-HT overflow obtained by increasing the stimulation frequency from 1 Hz to 5 Hz, which is due to an increase in terminal 5-HT autoreceptor activation at the higher frequency, was not altered by either toxin. The enhancing effect of the 5-HT autoreceptor antagonist methiothepin (1 mumol/l) on stimulation-evoked [3H]5-HT overflow was not changed by either pretreatment. N-Ethylmaleimide inactivates Gi/o proteins by alkylation.(ABSTRACT TRUNCATED AT 250 WORDS)
Blier
P
P
Department of Psychiatry, McGill University, Montréal, Québec, Canada.
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D011985:Receptors, Serotonin; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D012701:Serotonin; D008735:5-Methoxytryptamine; D002772:Cholera Toxin; C047087:5-carboxamidotryptamine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005033:Ethylmaleimide