PMID- 8794826
OWN - NLM
STAT- MEDLINE
DCOM- 19961122
LR  - 20190722
IS  - 0194-911X (Print)
IS  - 0194-911X (Linking)
VI  - 28
IP  - 3
DP  - 1996 Sep
TI  - Vesicular monoamine transport inhibitors. Novel action at calcium channels to 
      prevent catecholamine secretion.
PG  - 414-20
AB  - Vesicular monoamine transport (VMAT) inhibitors, such as reserpine and 
      tetrabenazine, impair vesicular catecholamine storage in chromaffin cells and 
      sympathetic neurons, thereby lowering blood pressure. Here we describe a novel 
      action of VMAT inhibitors-blockade of L-type voltage-gated calcium channels-that 
      may also influence catecholamine release from both PC12 rat pheochromocytoma 
      cells and bovine adrenal chromaffin cells. When given alone, VMAT inhibitors 
      acutely release catecholamines from chromaffin cells in a dose-dependent fashion. 
      However, VMAT inhibitors block catecholamine secretion stimulated by either 
      nicotinic cholinergic agonists or cell membrane depolarization, each of which 
      rely on the opening of L-type channels; the inhibition was more potent after 
      long-term exposure to VMAT inhibitors (IC50 < 100 nmol/L). Reserpine blocked 
      nicotinic-stimulated catecholamine release from neurite-bearing PC12 cells. 
      Reserpine also antagonized catecholamine release triggered by combined membrane 
      depolarization and the dihydropyridine L-type channel agonist Bay K8644, and 
      reserpine blocked cellular uptake of extracellular 45Ca2+ in response to 
      nicotine. Taken together, these results indicate that VMAT inhibitors are also 
      antagonists at L-type voltage-gated calcium channels. Classic L-type channel 
      antagonists (verapamil or nifedipine) also exhibited the reciprocal actions; 
      acutely, they released norepinephrine from chromaffin cells, and chronically, 
      they depleted cellular catecholamine stores, albeit with inferior molar potency 
      to reserpine (IC50 < 1 nmol/L). We conclude that VMAT inhibitors and L-type 
      calcium channel antagonists exert reciprocal inhibitory actions on each other's 
      more classic pharmacological targets. Furthermore, these novel actions are seen 
      at concentrations of these compounds frequently taken to be specific in vitro and 
      likely to occur during antihypertensive treatment in vivo.
FAU - Mahata, M
AU  - Mahata M
AD  - Department of Medicine, University of California, San Diego 92161, USA.
FAU - Mahata, S K
AU  - Mahata SK
FAU - Parmer, R J
AU  - Parmer RJ
FAU - O'Connor, D T
AU  - O'Connor DT
LA  - eng
GR  - N01NIMH20003/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 8B1QWR724A (Reserpine)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - Z9O08YRN8O (Tetrabenazine)
SB  - IM
MH  - Adrenal Glands/cytology/drug effects/metabolism
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels/*drug effects
MH  - Cattle
MH  - Chromaffin System/cytology/metabolism
MH  - Membrane Glycoproteins/*antagonists & inhibitors
MH  - *Membrane Transport Proteins
MH  - *Neuropeptides
MH  - Norepinephrine/*antagonists & inhibitors/metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Reserpine/*pharmacology
MH  - Tetrabenazine/*pharmacology
MH  - Vesicular Biogenic Amine Transport Proteins
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
AID - 10.1161/01.hyp.28.3.414 [doi]
PST - ppublish
SO  - Hypertension. 1996 Sep;28(3):414-20. doi: 10.1161/01.hyp.28.3.414.