Pharmacological and biochemical characterization of the D-1 dopamine receptor mediating acetylcholine release in rabbit retina

Journal Article · Tue Dec 01 00:00:00 EST 1987 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5363117

Hensler, J G; Cotterell, D J; Dubocovich, M L

Superfusion with dopamine (0.1 microM-10 mM) evokes calcium-dependent (/sup 3/H)acetylcholine release from rabbit retina labeled in vitro with (/sup 3/H)choline. This effect is antagonized by the D-1 dopamine receptor antagonist SCH 23390. Activation or blockade of D-2 dopamine, alpha-2 or beta receptors did not stimulate or attenuate the release of (/sup 3/H)acetylcholine from rabbit retina. Dopamine receptor agonists evoke the release of (/sup 3/H)acetylcholine with the following order of potency: apomorphine less than or equal to SKF(R)82526 < SKF 85174 < SKF(R)38393 less than or equal to pergolide less than or equal to dopamine (EC50 = 4.5 microM) < SKF(S)82526 less than or equal to SKF(S)38393. Dopamine receptor antagonists inhibited the dopamine-evoked release of (/sup 3/H)acetylcholine: SCH 23390 (IC50 = 1 nM) < (+)-butaclamol less than or equal to cis-flupenthixol < fluphenazine < perphenazine < trans-flupenthixol < R-sulpiride. The potencies of dopamine receptor agonists and antagonists at the dopamine receptor mediating (/sup 3/H)acetylcholine release is characteristic of the D-1 dopamine receptor. These potencies were correlated with the potencies of dopamine receptor agonists and antagonists at the D-1 dopamine receptor in rabbit retina as labeled by (/sup 3/H)SCH 23390, or as determined by adenylate cyclase activity. (/sup 3/H)SCH 23390 binding in rabbit retinal membranes was stable, saturable and reversible. Scatchard analysis of (/sup 3/H)SCH 23390 saturation data revealed a single high affinity binding site (Kd = 0.175 +/- 0.002 nM) with a maximum binding of 482 +/- 12 fmol/mg of protein. The potencies of dopamine receptor agonists to stimulate (/sup 3/H)acetylcholine release were correlated with their potencies to stimulate adenylate cyclase (r = 0.784, P less than .05, n = 7) and with their affinities at (/sup 3/H)SCH 23390 binding sites (r = 0.755, P < .05, n = 8).

• Research Organization: Northwestern Univ. Medical School, Chicago, IL
• OSTI ID: 5363117
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Vol. 243:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
SECRETION
CYCLASES
ENZYME ACTIVITY
DOPAMINE
BIOCHEMICAL REACTION KINETICS
RECEPTORS
CHOLINE
IN VITRO
RABBITS
RETINA
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
BODY AREAS
CARDIOTONICS
CARDIOVASCULAR AGENTS
DRUGS
ENZYMES
ESTERS
EYES
FACE
HEAD
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
LYASES
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PHENOLS
POLYPHENOLS
PROTEINS
QUATERNARY COMPOUNDS
REACTION KINETICS
SENSE ORGANS
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques