PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 6175845

Ionic modulation of alpha-adrenoceptors.

H Glossmann·F Lübbecke·P Bellemann·E L Sattler·G Doell
View original source ↗Export metadata ↓

Abstract

Effects of cations and nucleotides on the in vivo binding properties of alpha-adrenoceptors in rat cerebral cortex membranes are described. Na+ ion converts a large fraction alpha-adrenoceptors in the absence or presence of Mg2+ into a low affinity state. The effects of 10 mM Na+ can be observed in 250 mM Tris-HCL buffer. It is suggested that alpha 2-adrenoceptor agonists alter the affinity of Na+ for a receptor-associated membrane component. alpha 2-Adrenoceptors are linked to guanylnucleotide binding proteins, which may be involved in signal transfer. These sites are altered in their nucleotide binding properties by pretreatment of the membranes with a medium that allows for ADP ribosylation or/and phosphorylation. alpha 1-Adrenoceptors were probed with a new, high affinity ligand, 125J-HEAT. 125J-HEAT binds (30 degrees C) with Kd values between 6 and 8 pM to alpha 1-adrenoceptors if Na+ slows down the dissociation of 125J-HEAT in comparison with MG2+. Na+ as well as Mg2+ reverse the inhibitory action of phosphatidic acid on the alpha 1-adrenoceptors labeled by 125J-HEAT. Data on the target size, obtained by radiation inactivation, of the alpha 1-adrenoceptors are presented.

Explore related subjects

Adrenergic alpha-AntagonistsAnimalsCationsCerebral CortexClonidineIn Vitro TechniquesKineticsLigandsMembranesNucleotidesPhenethylaminesRatsReceptors, AdrenergicReceptors, Adrenergic, alphaTetralonesJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

H Glossmann, F Lübbecke, P Bellemann, E L Sattler, G Doell. 1982. Ionic modulation of alpha-adrenoceptors.. https://doi.org/10.1097/00005344-198200041-00011

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Differential effects of urapidil and doxazosin on heart rate.

OBJECTIVE: Although alpha-blockers are effective in lowering blood pressure, they may increase heart rate, an unwanted effect that could negatively affect outcome. However, the alpha-blocker urapidil might not increase heart rate due to its additional effect on 5-HT1A receptors. Therefore, we compared the effects of urapidil on heart rate with those of another alpha-blocker, doxazosin. METHODS: We performed a randomised, double-blind, placebo-controlled, cross-over study in 12 healthy males who received single oral doses of 60 mg urapidil, 4 mg doxazosin and placebo. Four hours following drug intake, heart rate and blood pressure were measured at rest and during exercise. RESULTS: Both doxazosin and urapidil decreased blood pressure to the same extent. Compared to placebo, resting heart rate was significantly increased by doxazosin (+25%, P < 0.05) but not by urapidil (+12%, n.s.). Resting heart rate with doxazosin was significantly higher than with urapidil (P < 0.05). Similarly, the rate pressure product (RPP) at rest was increased by doxazosin (+17%, P < 0.05) but not by urapidil (+6%, n.s.). CONCLUSIONS: We conclude that the increase in heart rate caused by urapidil is less pronounced than that with doxazosin, a property that might favour urapidil in the treatment of arterial hypertension. In addition, only doxazosin (but not urapidil) increased the RPP at rest, a finding that might be helpful to explain why this drug was never shown to improve outcome in the treatment of arterial hypertension.

Adrenergic alpha-Antagonists↗
PubMed2007

The synthetic TRH analogue taltirelin exerts modality-specific antinociceptive effects via distinct descending monoaminergic systems.

BACKGROUND AND PURPOSE: Exogenously administered thyrotropin-releasing hormone (TRH) is known to exert potent but short-acting centrally-mediated antinociceptive effects. We sought to investigate the mechanisms underlying these effects using the synthetic TRH analogue taltirelin, focusing on the descending monoaminergic systems in mice. EXPERIMENTAL APPROACH: The mice received systemic or local injections of taltirelin combined with either central noradrenaline (NA) or 5-hydroxytryptamine (5-HT) depletion by 6-hydroxydopamine (6-OHDA) or DL-p-chlorophenylalanine (PCPA), respectively, or blockade of their receptors. The degree of antinociception was determined using the tail flick and tail pressure tests. KEY RESULTS: Subcutaneously (s.c.) administered taltirelin exhibited dose-dependent antinociceptive effects in the tail flick and tail pressure tests. These effects appeared to be primarily supraspinally mediated, since intracerebroventricularly (i.c.v.) but not intrathecally (i.t.) injected taltirelin generated similar effects. Depletion of central NA abolished only the analgesic effect of taltirelin (s.c. and i.c.v.) on mechanical nociception. By contrast, depletion of central 5-HT abolished only its analgesic effect on thermal nociception. Intraperitoneal (i.p.) and i.t. injection of the alpha2-adrenoceptor antagonist yohimbine respectively reduced the analgesic effect of taltirelin (s.c. and i.c.v.) on mechanical nociception. By contrast, the 5-HT1A receptor antagonist WAY-100635 (i.p. and i.t.) reduced the effect of taltirelin (s.c. and i.c.v.) on thermal nociception. Neither the 5-HT2 receptor antagonist ketanserin nor the opioid receptor antagonist naloxone altered the antinociceptive effect of taltirelin. CONCLUSIONS AND IMPLICATIONS: These findings suggest that taltirelin activates the descending noradrenergic and serotonergic pain inhibitory systems, respectively, to exert its analgesic effects on mechanical and thermal nociception.

Adrenergic alpha-Antagonists↗
PubMed2007

Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats.

Intraspinal microstimulation (ISMS) through a single microelectrode can induce locomotion in cats spinalized at T(13) 1 wk before (untrained) or after 3-5 wk of treadmill training. Here we study the optimal parameters of ISMS and the characteristics of locomotion evoked. ISMS was applied in the dorsal region of segments L(3)-S(1) at different lateralities (midline to 2.5 mm) and after an intravenous injection of clonidine (noradrenergic agonist). Kinematics and electromyographic recordings were used to characterize locomotion. ISMS could induce a bilateral locomotor pattern similar to that obtained with perineal stimulation, and the characteristics of locomotion varied according to the spinal segment stimulated. Mechanisms by which ISMS could evoke locomotion were then investigated by stimulating, inactivating, or lesioning different spinal structures. Dorsal root stimulation (DRS), just like ISMS, could evoke a variety of ipsi- and bilateral nonlocomotor movements as well as locomotor responses. This suggests that sensory afferent pathways are involved in the production of locomotion by ISMS. Microinjections of yohimbine (noradrenergic antagonist) in L(3) and L(4) segments or a complete second spinal lesion at L(3)-L(4) abolished all locomotor activity evoked by ISMS applied at more caudal segments. Progressive dorsoventral spinal lesions at L(3) or L(4) and restricted ventral lesions at L(4) further suggest that the integrity of the ventral or ventrolateral funiculi as well as the L(3)-L(4) segments are critical for the induction of locomotion by ISMS at L(5) to S(1) or by DRS at these caudal segments.

Adrenergic alpha-Antagonists↗