Dopamine Di and

Momiyama, T, Nao5uiki, T and Saso, M (1993) A mechanism underl5dng dopamine Di and D2 receptor-mediated inhibition of dopaminergic neurons in the ventral tegmental area in vitro. Br. J. Pharmacol. 109 933-940. 

Gs Noradrenaline and fi2 Dopamine Di and D5 Histamine H2 Serotonin 5-HT4 Stimulates adenylate cyclase increasing the concentration of cAMP (cyclic-adenosine-3, 5 -monophosphate)... 

Fig. 7.4 Structures of compounds used in competitive MS binding assays for dopamine Di and D2 receptors.

Umemiya M, Berger AJ (1995) Presynaptic inhibition by serotonin of glycinergic inhibitory synaptic currents in the rat brain stem. J Neurophysiol 73 1192-1201 Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E (2000) Distinct functions of the two isoforms of dopamine D2 receptors. Nature 408 199-203 Vanderschuren LJ, Wardeh G, De Vries TJ, Mulder AH, Schoffelmeer AN (1999) Opposing role of dopamine Di and D2 receptors in modulation of rat nucleus accumbens noradrenaline release. J Neurosci 19 4123-31... 

Ridray S, Griffon N, Mignon V, Souil E, Carboni S, Diaz J, Schwartz JC, Sokoloff P (1998) Coexpression of dopamine Di and D3 receptors in islands of Calleja and shell of nucleus accumbens of the rat opposite and synergistic functional interactions. Eur J Neurosci 70 1676-1686. 

Vincent SL, Khan Y, Benes FM (1993) Cellular distribution of dopamine Di and D2 receptors in rat medial prefrontal cortex. J Neurosci 75 2551-2564. 

Bergman J, Kamien JB, Spealman RD (1990) Antagonism of cocaine self-administration by selective dopamine DI and D2 antagonists. Behav Pharmacol 1 355-363. 

Bowden C, Theodorou AE, Cheetham SC, Lowther S, Katona CL, Crompton MR, Horton RW (1997) Dopamine Di and D2 receptor binding sites in brain samples from depressed suicides and controls. Brain Res 752 227-233. 

Joyce JN, Lexow N, Bird E, Winokur A (1988) Organization of dopamine Di and D2 receptors in human striatum receptor autoradiographic studies in Huntington s disease and schizophrenia. Synapse 2 546-557. 

Metoclopramide has inhibitory effects on dopamine Di and D2 receptors, which influences its prokinetic activity and CNS side effects. 

Phenothiazines primariiy biock postsynaptic neurotransmission by binding to dopamine (Di and D2), muscarinic, histamine Hj, and serotonergic 5-HT2 receptors. Phenothiazines also possess peripheral a-adrenergic receptor blockade and quinidine-like cardiac effects. Phenothiazines may also lower the seizure threshold. 

Fadda P, Martellotta MC, De Montis MG, Gessa GE, Fratta W. Dopamine DI and opioid receptor binding changes in the limbic system of sleep deprived rats. Neurochem Int 1992 20 153S-156S. 

A comprehensive list of synthesized labeled receptor ligands is outside the scope of this chapter. Most attention has been focused on ligands for the dopamine-Di and D2 receptors. 

Waddington, JL (1989) Functional interactions between Di and D2 dopamine receptor systems their role in the regulation of psychomotor behaviour, putative mechanisms and clinical relevance. J. Psychopharm. 3 54-63. 

Dopamine has been implicated in a number of psychiatric conditions of which schizophrenia and the affective disorders are the most widely established. Five major subtypes of dopamine receptors have now been cloned. These are divided into two main groups, and D2 respectively. The receptors consist of Di and D5 types and are positively linked to the adenylate cyclase second messenger system, while the D2 group consists of the D2, D3 and D4 receptors which are negatively linked to the adenylate cyclase system. 

Fig. 7.5 Schematic flowchart of the competitive MS-binding assay quantifying the nonbound marker employed for dopamine Di receptors. After incubation of the target (Di receptor) in presence of the marker (SCH 23390) and a test compound, the binding samples are centrifuged to separate bound from nonbound marker. The nonbound marker in the resulting supernatant is quantified by LC-ESI-MS/MS without further sample preparation.

Di-receptors (comprising subtypes Di and D5) and D2-receptors (comprising subtypes D2, D3, and D4). The aforementioned actions are mediated mainly by D2 receptors. When given by infusion, dopamine causes dilation of renal and splanchnic arteries. This effect is mediated by Di receptors and is utilized in the treatment of cardiovascular shock and hypertensive emergencies by infusion of dopamine and fenoldopam, respectively. At higher doses, Pi-adrenoceptors and, finally, a-receptors are activated, as evidenced by cardiac stimulation and vasoconstriction, respectively. 

A single in vivo cocaine administration abolishes endocannabinoid-depen-dent LTD. This effect of cocaine was not present in mice lacking Di dopamine receptors and was blocked by a selective Di receptor and NMDA receptor antagonist, suggesting the involvement of D i and NMDA receptors (Fourgeaud et al. 2004). 

A PET study using selective tracers for striatal dopamine Di ([ C]NNC 756) and striatal dopamine D2 ([ C]raclopride) receptors showed that while striatal D2 receptors were unaffected in patients with AD, striatal Di receptors were reduced by 14% in patients with AD compared with healthy age-matched controls [43]. At present, no F-labeled dopamine Di tracers have been validated for human PET studies. 

The answer is b. (Hardman, pp 282-283.) Central dopamine receptors are divided into Di and D2 receptors. Antipsychotic activity is better correlated to blockade of D2 receptors. Haloperidol, a potent antipsychotic, selectively antagonizes at D2 receptors. Phenothiazine derivatives, such as chlorpromazine, fluphenazine, and promethazine, are not selective for D2 receptors. Bromocriptine, a selective D2 agonist, is useful in the treatment of parkinsonism and hyperprolactinemia. It produces fewer adverse reactions than do nonselective dopamine receptor agonists. 

Acquas, Elio, and Gaetano Di Chiara. 1992. "Depression of Mesolimbic Dopamine Transmission and Sensitization to Morphine During Opiate Abstinence." Journal of Neurochemistry 58 1620-25. 

---