Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone
Journal Article
·
· Proceedings of the National Academy of Sciences of the United States of America; (USA)
- Univ. of Alberta, Edmonton (Canada)
The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca{sup 2+} channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca{sup 2+} currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca{sup 2+} channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca{sup 2+} in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues PTH can act as an endogenous blocker of Ca{sup 2+} entry.
- OSTI ID:
- 6700159
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:2; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BIOELECTRICITY
CALCIUM COMPOUNDS
CATIONS
CATTLE
CHARGED PARTICLES
CHEMICAL REACTIONS
CROSS-LINKING
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ELECTRIC POTENTIAL
ELECTRICITY
FLUORESCENCE
HORMONES
INHIBITION
IONS
LUMINESCENCE
MAMMALS
MEMBRANE TRANSPORT
MICE
MUSCLES
PARATHORMONE
PEPTIDE HORMONES
PHARMACOLOGY
POLYMERIZATION
RODENTS
RUMINANTS
TUMOR CELLS
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BIOELECTRICITY
CALCIUM COMPOUNDS
CATIONS
CATTLE
CHARGED PARTICLES
CHEMICAL REACTIONS
CROSS-LINKING
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ELECTRIC POTENTIAL
ELECTRICITY
FLUORESCENCE
HORMONES
INHIBITION
IONS
LUMINESCENCE
MAMMALS
MEMBRANE TRANSPORT
MICE
MUSCLES
PARATHORMONE
PEPTIDE HORMONES
PHARMACOLOGY
POLYMERIZATION
RODENTS
RUMINANTS
TUMOR CELLS
VERTEBRATES