Pituitary Ca/sup 2 +/ channels: blockade by conventional and novel Ca/sup 2 +/ antagonists

Journal Article · Wed Jul 01 04:00:00 EDT 1987 · Am. J. Physiol.; (United States)

OSTI ID:6143081

Enyeart, J J; Sheu, S S; Hinkle, P M

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), Journal Name: Am. J. Physiol.; (United States) Vol. 253:1; ISSN AJPHA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
AMINES
ANIMALS
ANTIGENS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CATIONS
CHARGED PARTICLES
DAYS LIVING RADIOISOTOPES
ENDOCRINE GLANDS
EVEN-ODD NUCLEI
GLANDS
GONADOTROPINS
HETEROCYCLIC COMPOUNDS
HORMONES
INTERMEDIATE MASS NUCLEI
IONS
ISOTOPES
LTH
MAMMALS
MATERIALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHARMACOLOGY
PHYSIOLOGY
PIPERIDINES
PITUITARY GLAND
PITUITARY HORMONES
PYRIDINES
RADIOISOTOPES
RATS
RODENTS
SECRETION
TOXIC MATERIALS
TOXINS
UPTAKE
VERTEBRATES