M1 muscarinic receptors contribute to, whereas M4 receptors inhibit, dopamine D1 receptor-induced [3H]-cyclic AMP accumulation in rat striatal slices.
In rat striatal slices labelled with [(3)H]-adenine and in the presence of 1 mM 3-isobutyl-1-methylxantine (IBMX), cyclic [(3)H]-AMP ([(3)H]-cAMP) accumulation induced by the dopamine D(1) receptor agonist SKF-81297 (1 microM; 177 +/- 13% of basal) was inhibited by the general muscarinic agonist carbachol (maximum inhibition 72 +/- 3%, IC(50) 0.30 +/- 0.06 microM). The muscarinic toxin 7 (MT-7), a selective antagonist at muscarinic M(1) receptors, reduced the effect of SKF-81297 by 40+/-7% (IC(50) 251+/- 57 pM) and enhanced the inhibitory action of a submaximal (1 microM) concentration of carbachol (69 +/- 4% vs. 40 +/- 7% inhibition, IC(50) 386 +/- 105 pM). The toxin MT-1, agonist at M(1) receptors, stimulated [(3)H]-cAMP accumulation in a modest but significant manner (137 +/- 11% of basal at 400 nM), an action additive to that of D(1) receptor activation and blocked by MT-7 (10 nM). The effects of MT-7 on D(1) receptor-induced [(3)H]-cAMP accumulation and the carbachol inhibition were mimicked by the PKC inhibitors Ro-318220 (200 nM) and Gö-6976 (200 nM). Taken together our results indicate that in addition to the inhibitory role of M(4) receptors, in rat striatum acetylcholine stimulates cAMP formation through the activation of M(1 )receptors and PKC stimulation.
Sánchez-Lemus
Enrique
E
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, México, DF, México. jaarias@fisio.cinvestav.mx
Arias-Montaño
José-Antonio
JA
D000470:Alkaloids / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D002217:Carbachol / Q000378:metabolism; D018679:Cholinergic Agonists / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism; D005663:Furans / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism; D019832:N-Methylscopolamine / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D043588:Receptor, Muscarinic M4 / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
D000470:Alkaloids; D001552:Benzazepines; D018679:Cholinergic Agonists; D018491:Dopamine Agonists; D005663:Furans; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D010276:Parasympatholytics; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043588:Receptor, Muscarinic M4; D017447:Receptors, Dopamine D1; D010890:Pirenzepine; C067113:SK&F 81297; D002217:Carbachol; D000242:Cyclic AMP; D011493:Protein Kinase C; C048172:himbacine; D019832:N-Methylscopolamine