Abstract

A "caged" analogue of the α-adrenergic receptor agonist phenylephrine (PE) was prepared by exploiting the 2-nitrobenzyl protecting group and using a synthetic procedure developed to permit preferential derivatization at the amino group. On isolated adult rat mesenteric arterioles, caged-PE had no measurable effects at concentrations up to 100 μM; 0.5-ms light flashes in the presence of caged-PE, however, produced marked and dose-dependent vasoconstriction. Flash-induced vasoconstrictions were blocked by the α-receptor antagonist phentolamine and were unaffected by the β-receptor antagonist propranolol, indicating that the light-induced responses reflect the selective activation of α-adrenergic receptors. After a single flash, a large transient decrease in vessel diameter was recorded, and in most vessels, this was followed by a smaller, sustained constriction. The sustained component of the contraction was selectively eliminated when Ca2+ was removed from the bath, which suggests that different mechanisms underlie the transient and the sustained responses to PE. The responses to single flashes of varying intensities occurred with a mean latency of 460 ms, which is consistent with the intermediacy of several steps between α-receptor activation and contraction. We anticipate that it will be possible to extend this approach to develop caged analogues of other neurotransmitters for mechanistic and kinetic studies.

Original languageEnglish
Pages (from-to)5199-5203
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number11
StatePublished - Jun 1 1993

Keywords

  • Calcium
  • Vascular smooth muscle
  • α-adrenergic receptor

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