α1Adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle

Chide Han, Peter W. Abel, Kenneth P. Minneman

Research output: Contribution to journalArticlepeer-review

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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 α1-adrenoceptors to increase cytosolic Ca2+ and promote smooth muscle contraction1. In many cells activation of α1-adrenoceptors causes formation of inositol 1,4,5-trisphosphate which promotes Ca2+ release from intracellular stores2,3. 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 phosphates4,5 or release of stored intracellular Ca2+ (ref. 3). However α1- adrenoceptors have recently been shown to have different pharmacological properties in different tissues6-9, and it has been proposed that different α1-adrenoceptor subtypes may control mobilization of intracellular Ca2+ and gating of extracellular Ca2+ influx7,9,10-12. We here report evidence for two subtypes of α1-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 Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)333-335
Number of pages3
JournalNature
Volume329
Issue number6137
DOIs
StatePublished - Jan 1 1987
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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