Alpha 1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle

Nature. 1987 Sep 24-30;329(6137):333-5. doi: 10.1038/329333a0.

Abstract

Receptor-mediated increases in intracellular Ca2+ levels can be caused by release from intracellular organelles and/or influx from the extracellular fluid. Noradrenaline (NA) released from sympathetic nerves acts on alpha 1-adrenoceptors to increase cytosolic Ca2+ and promote smooth muscle contraction. In many cells activation of alpha 1-adrenoceptors causes formation of inositol 1,4,5-trisphosphate which promotes Ca2+ release from intracellular stores. The mechanism by which receptor activation opens cell surface Ca2+ channels is not known, although in some cases it may be secondary to formation of inositol phosphates or release of stored intracellular Ca2+ (ref. 3). However, alpha 1-adrenoceptors have recently been shown to have different pharmacological properties in different tissues, and it has been proposed that different alpha 1-adrenoceptor subtypes may control mobilization of intracellular Ca2+ and gating of extracellular Ca2+ influx. We here report evidence for two subtypes of alpha 1-adrenoceptors which cause contractile responses through different molecular mechanisms. One subtype stimulates inositol phosphate (InsP) formation and causes contractions which are independent of extracellular Ca2+, and the other does not stimulate inositol phosphate formation and causes contractions which require the influx of extracellular Ca2+ through dihydropyridine-sensitive channels. These results suggest that neurotransmitters and hormones may control Ca2+ release from intracellular stores and influx through voltage-gated membrane channels through distinct receptor subtypes.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Calcium / metabolism*
  • Dihydropyridines*
  • Hippocampus / physiology
  • Inositol Phosphates / biosynthesis
  • Ion Channels / drug effects
  • Ion Channels / physiology
  • Liver / physiology
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / metabolism*
  • Phenethylamines / metabolism
  • Pyridines / pharmacology
  • Rats
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology*
  • Spleen / physiology
  • Tetralones*
  • Vas Deferens / physiology

Substances

  • Adrenergic alpha-Antagonists
  • Dihydropyridines
  • Inositol Phosphates
  • Ion Channels
  • Phenethylamines
  • Pyridines
  • Receptors, Adrenergic, alpha
  • Tetralones
  • BE 2254
  • 1,4-dihydropyridine
  • Calcium