Parathyroid hormone selectively inhibits L-type calcium channels in single vascular smooth muscle cells of the rat.
1. The active synthetic N-terminal fragment of bovine parathyroid hormone, bPTH-(1-34) at a concentration of 1 microM, decreased the peak amplitude of the long-lasting (L-type) calcium channel current by 37% (n = 14, P less than 0.01) in rat tail artery smooth muscle cells. By contrast, this fragment of parathyroid hormone (PTH) (1 microM) had no effect on the transient (T-type) calcium channel current in the same cell preparation. 2. The inhibitory effect of bPTH-(1-34) on L-channel currents was reversible and could be antagonized by the L-channel agonist, Bay K 8644. In contrast, bPTH-(1-34) inhibited Bay K 8644-induced amplification of L-channel currents. 3. The inhibitory effect of bPTH-(1-34) on L-Channel currents was dose dependent with a threshold concentration of less than 10(-7), and voltage dependent with increased inhibition at more positive holding potentials. However, this effect of bPTH-(1-34) was not dependent on different pulse lengths or interpulse intervals. 4. The kinetics of deactivation of L-channel currents were not changed although the instantaneous amplitude of the L-channel tail current was reduced by bPTH-(1-34). 5. Application of bPTH-(1-34) antagonists (10(-6) M-bPTH-(3-34) and 10(-5) M-bPTH-(7-34] did not result in any significant change in the magnitude of L-channel currents (n = 15 and n = 7, respectively). 6. Pre-incubation of cells with bPTH-(3-34) for more than 15 min abolished the inhibitory effect of bPTH-(1-34) on L-channel currents. 7. The present study provides direct evidence to demonstrate the PTH, an endogenous circulating hormone, is a selective inhibitor of L-channel currents in vascular smooth muscle cells.
Wang
R
R
Department of Physiology, University of Alberta, Edmonton, Canada.
Karpinski
E
E
Pang
P K
PK
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide
D015220:Calcium Channels; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester