Ionic mechanism of dopaminergic and muscarinic auto- and heteroreceptor activation in superfused striatal slices: role of extracellular chloride.
The Cl dependency of agonist-induced ionic mechanisms involved in the receptor-mediated modulation of electrically stimulated release of dopamine (DA) and acetylcholine (ACh) was examined in superfused rabbit striatal slices prelabeled with [3H] DA (3,4-[8-3H]dihydroxyphenylethylamine) and [14C]choline ([ methyl-14C]choline Cl). Cl- was substituted in the superfusion medium to varying degrees with the impermeant anions isethionate, methanesulfonate or gluconate. The sodium concentration was held constant. Apomorphine (30 nM), a DA receptor agonist, inhibited the stimulation-evoked (1 Hz, 2 min) release of both DA and ACh in Krebs-Ringer-bicarbonate medium (KRB; 125.4 mM Cl-). The inhibitory effects of the agonist were not altered significantly in media containing 66.4 mM Cl-. In 7.4 mM Cl- medium (isethionate replacement), apomorphine-induced inhibition of DA release was reduced (40% inhibition vs. 67% inhibition in KRB). Similarly, apomorphine inhibition of ACh release was lowered from 38% in KRB to 25% in 7.4 mM Cl-. The muscarinic receptor agonist carbachol (10 microM) inhibited the stimulation-evoked release of ACh while enhancing the evoked release of DA in normal Cl- (125.4 mM) medium. Inhibition of ACh release was not altered in 66.4 mM Cl- media but was increased in 7.4 mM Cl- (63% inhibition in low Cl- vs. 50% in KRB). The enhancing effects of carbachol on stimulated DA release were potentiated in 66.4 mM Cl- (88% enhancement vs. 57% in KRB), whereas no change in the agonist effect was observed in the lower Cl- medium (7.4 mM Cl-).(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D011817:Rabbits; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D002712:Chlorides; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D002217:Carbachol; D001058:Apomorphine; D000109:Acetylcholine; D004298:Dopamine