Pituitary Ca/sup 2 +/ channels: blockade by conventional and novel Ca/sup 2 +/ antagonists
The authors have identified several new agents that block Ca/sup 2 +/ channels in the rat pituitary GH/sub 4/C/sub 1/ cell line. These drugs, which include the diphenylbutylpiperidine antipsychotic pimozide, the calmodulin antagonist calmidazolium, and the steroidal Na/sup +/ channel toxin veratridine, were compared with several conventional Ca/sup 2 +/ antagonists in /sup 45/Ca/sup 2 +/ uptake, prolactin secretion, and whole cell patch voltage-clamp experiments. Pimozide, the most potent of these novel Ca/sup 2 +/ antagonists, inhibited depolarization-dependent /sup 45/Ca/sup 2 +/ uptake and prolactin secretion half maximally at a concentration of 100 nM, whereas calmidazolium and veratridine produced 50% inhibition at concentrations of 500 nM and 1 ..mu..M. In comparison, the three organic Ca/sup 2 +/ antagonists nitrendipine, verapamil, and diltiazem blocked /sup 45/Ca/sup 2 +/ uptake half maximally at concentrations of 2.5 nM, 1 ..mu..M, and 2.5 ..mu..M, respectively. All of the antagonists inhibited Ca/sup 2 +/ uptake and prolactin secretion stimulated by the dihydropyridine Ca/sup 2 +/ agonist BAY-K 8644 less potently than KCl-stimulated responses. In patch-clamp experiments, pimozide, veratridine, and nitrendipine blocked Ca/sup 2 +/ current through the slowly inactivating Ca/sup 2 +/ channels of GH/sub 4/C/sub 1/ cells. These results demonstrate that Ca/sup 2 +/ channels in an endocrine cell line can be blocked by a variety of molecules including sodium channel toxins and calmodulin antagonists. The data extend the pharmacological similarity between Ca/sup 2 +/ channels in pituitary and other excitable cells and suggest a structural similarity among several cellular proteins.
- Research Organization:
- Univ. of Rochester School of Medicine and Dentistry, NY (USA)
- OSTI ID:
- 6143081
- Journal Information:
- Am. J. Physiol.; (United States), Vol. 253:1
- Country of Publication:
- United States
- Language:
- English
Similar Records
Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary
Dihydropyridine-sensitive calcium channel activity related to prolactin, growth hormone, and luteinizing hormone release from anterior pituitary cells in culture: interactions with somatostatin, dopamine, and estrogens
Related Subjects
CALCIUM 45
UPTAKE
PITUITARY GLAND
PHYSIOLOGY
PYRIDINES
PHARMACOLOGY
CALCIUM COMPOUNDS
CATIONS
LTH
PIPERIDINES
RATS
SECRETION
TOXINS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
AMINES
ANIMALS
ANTIGENS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CHARGED PARTICLES
DAYS LIVING RADIOISOTOPES
ENDOCRINE GLANDS
EVEN-ODD NUCLEI
GLANDS
GONADOTROPINS
HETEROCYCLIC COMPOUNDS
HORMONES
INTERMEDIATE MASS NUCLEI
IONS
ISOTOPES
MAMMALS
MATERIALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
RADIOISOTOPES
RODENTS
TOXIC MATERIALS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques