PHARMACOLOGY OF HIGH-THRESHOLD CALCIUM CURRENTS IN GH(4)C(1) PITUITARY-CELLS AND THEIR REGULATION BY ACTIVATION OF HUMAN D-2 AND D-4 DOPAMINE-RECEPTORS

被引:32
作者
SEABROOK, GR
KNOWLES, M
BROWN, N
MYERS, J
SINCLAIR, H
PATEL, S
FREEDMAN, SB
MCALLISTER, G
机构
[1] Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, CM20 2QR, Terlings Park, Eastwick Road
关键词
DOPAMINE; D4 DOPAMINE RECEPTOR; DIHYDROPYRIDINE; CALCIUM CHANNEL CURRENT; PITUITARY; GH(4)C(1) CELLS;
D O I
10.1111/j.1476-5381.1994.tb13138.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The objective of this study was to characterize the pharmacology of calcium currents in GH(4)C(1) pituitary cells and determine whether activation of heterologously expressed human dopamine receptors can regulate their function. Human D-2(short), D-3 and D-4.2 receptor cDNA's were separately transfected into GH(4)C(1) cells and whole cell calcium currents were recorded by use of nystatin-perforated patch clamp techniques. 2 High-threshold calcium currents were antagonized in a biphasic manner by the dihydropyridine, nisoldipine. The half-maximally effective concentration for each site was 0.2 nM (pIC(50) = 9.78 +/- 0.21, n = 4) and 339 nM (pIC(50) = 6.47 +/- 0.12, n = 4). The component of current inhibited by 10 nM nisoldipine was also blocked by omega-conotoxin GVIA (30 +/- 9% at 30 nM, n = 6) or by omega-agatoxin IVA (34 +/- 7% at 100 nM, n = 4). 3 Activation of either D-2 or D-4 receptors by dopamine (10 mu M) or quinpirole (0.1 to 10 mu M) reduced the peak calcium current by ca. 20% in the majority of cells studied. No inhibition was observed in control or D-3 transfected GH(4)C(1) cell lines. 4 The mobilisation of intracellular calcium by thyrotropin releasing hormone in hD(4)-GH(4)C(1) cells was also studied using Fura-2 AM microspectrofluorimetry. Thyrotropin releasing hormone caused a concentration-dependent increase in calcium mobilisation with an EC(50) of 7 nM. D-4 receptor activation had no effect upon either basal or hormone-induced [Ca2+](i) transients. 5 These results demonstrate that GH(4)C(1) pituitary cells have at least two types of dihydropyridine-sensitive high-threshold calcium currents and that like D-2 receptors, human Dq receptors can also regulate calcium channel function.
引用
收藏
页码:728 / 734
页数:7
相关论文
共 38 条
[1]  
ALBERT PR, 1990, J BIOL CHEM, V265, P2098
[2]   SPECIFIC INDUCTION OF A FUNCTIONAL ENDOGENOUS D2 SHORT DOPAMINE RECEPTOR IN GH4C1 CELLS [J].
ALLARD, S ;
LAPOINTE, S ;
FALARDEAU, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 193 (02) :801-807
[3]   2 DISTINCT POPULATIONS OF CALCIUM CHANNELS IN A CLONAL LINE OF PITUITARY-CELLS [J].
ARMSTRONG, CM ;
MATTESON, DR .
SCIENCE, 1985, 227 (4682) :65-67
[4]   EFFECTS OF HYPOTHALAMIC PEPTIDES ON ELECTRICAL-ACTIVITY AND MEMBRANE CURRENTS OF PATCH PERFORATED CLAMPED GH3 ANTERIOR-PITUITARY-CELLS [J].
BARROS, F ;
DELGADO, LM ;
MACIA, C ;
DELAPENA, P .
FEBS LETTERS, 1991, 279 (01) :33-37
[5]  
CASTELLANO MA, 1993, MOL PHARMACOL, V44, P649
[6]   NIMODIPINE BLOCK OF CALCIUM CHANNELS IN RAT ANTERIOR-PITUITARY-CELLS [J].
COHEN, CJ ;
MCCARTHY, RT .
JOURNAL OF PHYSIOLOGY-LONDON, 1987, 387 :195-225
[7]   DUAL MODULATION OF K-CHANNELS BY THYROTROPIN-RELEASING-HORMONE IN CLONAL PITUITARY-CELLS [J].
DUBINSKY, JM ;
OXFORD, GS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (12) :4282-4286
[8]  
EINHORN L C, 1990, Society for Neuroscience Abstracts, V16, P382
[9]  
EINHORN LC, 1991, J NEUROSCI, V11, P3727
[10]  
FREEDMAN SB, 1994, J PHARMACOL EXP THER, V268, P417