Opioid receptors and inhibition of dopamine-sensitive adenylate cyclase in slices of rat brain regions receiving a dense dopaminergic input.
In slices of rat nucleus accumbens, olfactory tubercle, frontal cortex and mediobasal hypothalamus exposed to dopamine (DA), the activation of DA D1 receptors stimulated cyclic AMP (cAMP) formation whereas, in nucleus accumbens slices only, activation of D2 receptors appeared to inhibit D1 receptor-stimulated adenylate cyclase at the same time. Activation of mu-opioid receptors by [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO; 1 microM), but not of delta-opioid receptors by 1 microM [D-Pen2,D-Pen5]enkephalin (DPDPE), inhibited (by 35-40%) DA-stimulated cAMP production in slices of nucleus accumbens and olfactory tubercle. When adenylate cyclase was stimulated by selective D1 receptor activation, i.e. by DA in the presence of (-)-sulpiride, DPDPE reduced cAMP formation (by about 45%) in nucleus accumbens slices but not in slices of the other brain regions. The kappa-agonist, U 50,488, did not affect DA- or D1 receptor-stimulated adenylate cyclase activity in any of the brain regions. Preincubation of nucleus accumbens slices with the irreversible delta-ligand, fentanyl isothiocyanate (FIT; 1 microM), not only antagonized the inhibitory effect of DPDPE but also prevented the antagonism by naloxone of the inhibitory effect of DAMGO. Therefore, in nucleus accumbens opioids may inhibit DA-sensitive adenylate cyclase through activation of a mu/delta-opioid receptor complex, whereas in olfactory tubercle mu-receptors appear to mediate the inhibition of adenylate cyclase activity. Opioids do not seem to affect DA-stimulated cAMP formation in frontal cortex and mediobasal hypothalamus.
Heijna
M H
MH
Department of Pharmacology, Free University, Medical Faculty, Amsterdam, Netherlands.
Bakker
J M
JM
Hogenboom
F
F
Mulder
A H
AH
Schoffelmeer
A N
AN
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology* / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009833:Olfactory Pathways / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D004745:Enkephalins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004298:Dopamine