RATIONALE Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. OBJECTIVES Extending this work to beta 2 adrenergic systems in vitro and in vivo. METHODS Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction...

BACKGROUND In subjects with heart failure, angiotensin converting enzyme inhibitors exhibit mild systemic antiadrenergic effects, as deduced from treatment-related lowering of systemic venous norepinephrine levels. The effects of angiotensin converting enzyme inhibitors on cardiac adrenergic drive in subjects with heart failure has not previously been investigated. METHODS AND RESULTS In a pl...

In the isolated perfused hindlimb preparation of the dog, pressor responses to norepinephrine (NE) are mediated by postsynaptic alpha 1- and alpha 2-adrenergic receptors. Results obtained using preferential alpha 1- and alpha 2-adrenergic receptor antagonists suggest that the alpha 1-subtype is predominantly innervated while both alpha 1- and alpha 2-adrenergic receptor subtypes in vascular smo...

An azide analog, 2-[4-(4-azidobenzoyl)piperazin-1-yl]-4-amino-6, 7-dimethoxyquinazoline (CP59,430), of the highly selective alpha 1-adrenergic receptor antagonist prazosin was synthesized and its effects on rat hepatic membrane and affinity-purified alpha 1-adrenergic receptor preparations were examined. CP59,430 behaved as a competitive antagonist before photolysis. When the membrane or purifi...

The cDNA for the Syrian hamster alpha 1-adrenergic receptor has been cloned with oligonucleotides corresponding to the partial amino acid sequence of the receptor protein purified from DDT1MF-2 smooth muscle cells. The deduced amino acid sequence encodes a 515-residue polypeptide that shows the most sequence identity with the other adrenergic receptors and the putative protein product of the re...

Many studies have suggested that alpha-adrenergic receptors on vascular smooth muscle are heterogeneous and that both alpha 1- and alpha 2-adrenergic receptors can cause vasoconstriction when stimulated. We explored this hypothesis in normal humans by comparing the capacity of yohimbine, an alpha 2-adrenergic receptor antagonist, and prazosin, an alpha 1-adrenergic receptor agonist, with differ...

We evaluated the G protein selectivity of chimeric M1 and M2 muscarinic cholinergic receptors in which either the third intracellular (I3) loop or the N-terminal portion of this loop (the I3N peptide) was replaced by the corresponding sequence from the beta 1-adrenergic receptor. The chimeras retained agonist-dependent G protein regulatory activity, but were completely promiscuous among potenti...

High affinity agonist-binding (HAB) sites are formed from specific receptor interaction with guanine nucleotide-binding (Gi) proteins. To determine whether the release of endothelium-derived relaxing factor (EDRF) is regulated by specific receptor-Gi protein coupling, we treated bovine aortic endothelial cells with 100 ng/ml pertussis toxin (PTX) for 16 hours to effect receptor-Gi protein uncou...

BACKGROUND Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that alpha-adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol. METHODS AND RESULTS Forearm vascular resistance responses to isometric handgrip and cold pressor test were dete...