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 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.
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Han, C., Abel, P. & Minneman, K. α1Adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle. Nature 329, 333–335 (1987). https://doi.org/10.1038/329333a0
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DOI: https://doi.org/10.1038/329333a0
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