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Identification of a D 1 dopamine receptor, not linked to adenylate cyclase, on lactotroph cells
Author(s) -
Schoors Danny F.,
Vauquelin Georges P.,
Vos Hilde,
Smets Gerda,
Velkeniers Brigitte,
Vanhaelst Luc,
Dupont Alain G.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12354.x
Subject(s) - fenoldopam , endocrinology , medicine , spiperone , prolactin cell , sch 23390 , prolactin , dopamine receptor , receptor , agonist , biology , chemistry , dopamine , hormone
1 We studied the lactotroph cells of the rat by both in vivo and in vitro pharmacological techniques for the presence of D 1 ‐receptors. Both approaches revealed the presence of a D 2 ‐receptor, stimulated by quinpirole (resulting in an inhibition of prolactin secretion) and blocked by domperidone. 2 Administration of fenoldopam, the most selective D 1 ‐receptor agonist currently available, resulted in a dose‐dependent decrease of prolactin secretion in vivo (after pretreatment with α‐methyl‐ p ‐tyrosine) and in vitro (cultured pituitary cells). This increase was dose‐dependently blocked by the selective D 1 ‐receptor antagonist, SCH 23390, and although the effect of fenoldopam was less than that obtained by D 2 ‐receptor stimulation, these data suggest that a D 1 ‐receptor also controls prolactin secretion. 3 In order to detect the location of these dopamine receptors, autoradiographic studies were performed by use of [ 3 H]‐SCH 23390 and [ 3 H]‐spiperone as markers for D 1 and D 2 ‐receptors, respectively. Specific binding sites for [ 3 H]‐SCH 23390 were demonstrated. Fenoldopam dose‐dependently reduced [ 3 H]‐SCH 23390 binding, but had no effect on [ 3 H]‐spiperone binding. Immunocytochemical labelling of prolactin cells after incubation with [ 3 H]‐SCH 23390 revealed that the granulae and hence, D 1 binding sites were present on the lactotroph cells. 4 Radioligand binding studies performed on membranes from anterior pituitary cells revealed the presence of the D 2 ‐receptor (54 fmol mg −1 protein) with a K d of 0.58 n m for [ 3 H]‐spiperone, but failed to detect D 1 ‐receptors. 5 Finally, we studied the effect of dopamine and of fenoldopam on the adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) content of anterior pituitary cells. Although cyclic AMP increased upon prostacyclin administration, indicating an intact adenylate cyclase system, fenoldopam failed to increase the cyclic AMP production. 6 It is tempting to speculate that fenoldopam reduces prolactin secretion through interaction with a non‐cyclase‐linked D 1 ‐receptor on the lactotroph cells.