Cholecystokinin release from the rat caudate-putamen, cortex and hippocampus is increased by activation of the D1 dopamine receptor.
Studies were undertaken to examine the role of dopamine in the regulation of cholecystokinin (CCK) release in slices of the rat caudate-putamen (CP), a region where both neuroactive substances are abundant yet not extensively colocalized. It was found that dopamine, acting through a D1 dopamine receptor, is a major factor regulating CCK release in this tissue. Haloperidol and the selective D1 antagonist, SKF 83566, but not the D2 antagonist, sulpiride, inhibited potassium-evoked release from CP slices. Apomorphine enhanced both basal and potassium-evoked release, an effect which was reversed by (+/-)SKF 83566, but not by sulpiride. The D1 agonist, (+)SKF 38393, displayed agonist and antagonist activity in this system, whereas the D2 agonist, quinpirole, had no effect. Depletion of endogenous dopamine by pretreatment of animals with alpha-methyl-para-tyrosine decreased potassium-induced release by 45%, and in these animals, haloperidol no longer inhibited release. These dopaminergic agents altered CCK release in cortex and hippocampus in a similar fashion, although those tissues were less sensitive to their effects. These results suggest that dopamine, acting through D1 receptors, increases CCK release in CP, cortex and hippocampus. The results of previous studies showing that phorbol esters increase CCK release and that occupation of D1 receptors increases phosphoinositol turnover make it possible to hypothesize that dopamine, acting through D1 receptors, is increasing CCK release by increasing phosphoinositol turnover. Further studies will be required to verify this hypothesis and to determine whether dopamine is acting directly or indirectly to modulate CCK release.
Department of Pharmacological and Physiological Sciences, St. Louis University Medical School, Missouri.
J S
JS
Brog
M C
MC
Beinfeld
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002421:Caudate Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002766:Cholecystokinin / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D011699:Putamen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D019805:alpha-Methyltyrosine
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D008781:Methyltyrosines; D011954:Receptors, Dopamine; D019805:alpha-Methyltyrosine; D002766:Cholecystokinin; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine