The adrenergic receptors play a key role in the modulation of sympathetic nervous system activity as well as a site of action for many therapeutic agents. The alpha1-adrenergic receptor subtypes (alpha1A-, alpha1B-, alpha1D) are the prime mediators of smooth muscle contraction and hypertrophic growth, but their characterization in both binding and function have lagged the other adrenergic family members. Although they are derived from a related ancestral gene and all nine adrenergic receptor family members bind the endogenous ligands, epinephrine and norepinephrine, with roughly similar affinities, there are major differences in the mode of binding, second messenger utilization, and physiological effects of the alpha1-subtypes compared with beta- or alpha2-subtypes. Here, we review the recent literature on aspects of its binding pocket and how it differs from the beta-adrenergic receptor paradigms. We also review the signaling components and aspects of its function and provide new insights into its roles in smooth muscle, growth, neurological, and cardiovascular function.

Alpha1-adrenergic receptors: new insights and directions

A framework for the study of self- and family management of chronic conditions

In task-based language assessment (TBLA) language use is observed in settings that are more realistic and complex than in discrete skills assessments, and which typically require the integration of topical, social and/or pragmatic knowledge along with knowledge of the formal elements of language. But designing an assessment is not accomplished simply by determining the settings in which performance will be observed. TBLA raises questions of just how to design complex tasks, evaluate students’ performances and draw valid conclusions therefrom. This article examines these challenges from the perspective of ‘evidence-centred assessment design’. The main building blocks are student, evidence and task models, with tasks to be administered in accordance with an assembly model. We describe these models, show how they are linked and assembled to frame an assessment argument and illustrate points with examples from task-based language assessment.

Design and analysis in task-based language assessment

To investigate the physiological role of the α1D-adrenergic receptor (α1D-AR) subtype, we created mice lacking the α1D-AR (α1D ‐/‐) by gene targeting and characterized their cardiovascular function. In α1D ‐/‐ mice, the RT-PCR did not detect any transcript of the α1D-AR in any tissue examined, and there was no apparent upregulation of other α1-AR subtypes. Radioligand binding studies showed that α1-AR binding capacity in the aorta was lost, while that in the heart was unaltered in α1D ‐/‐ mice. Non-anesthetized α1D ‐/‐ mice maintained significantly lower basal systolic and mean arterial blood pressure conditions, relative to wild-type mice, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. Besides hypotension, the pressor responses to phenylephrine and norepinephrine were decreased by 30‐40% in α1D ‐/‐ mice. Furthermore, the contractile response of the aorta and the pressor response of isolated perfused mesenteric arterial beds to α1-AR stimulation were markedly reduced in α1D ‐/‐ mice. We conclude that the α1D-AR participates directly in sympathetic regulation of systemic blood pressure by vasoconstriction.

/pdf/the-a1d-adrenergic-receptor-directly-regulates-arterial-1jungcqvek.pdf

The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

Catecholamines and alpha(1)-adrenergic receptors (alpha(1)-ARs) cause cardiac hypertrophy in cultured myocytes and transgenic mice, but heart size is normal in single KOs of the main alpha(1)-AR subtypes, alpha(1A/C) and alpha(1B). Here we tested whether alpha(1)-ARs are required for developmental cardiac hypertrophy by generating alpha(1A/C) and alpha(1B) double KO (ABKO) mice, which had no cardiac alpha(1)-AR binding. In male ABKO mice, heart growth after weaning was 40% less than in WT, and the smaller heart was due to smaller myocytes. Body and other organ weights were unchanged, indicating a specific effect on the heart. Blood pressure in ABKO mice was the same as in WT, showing that the smaller heart was not due to decreased load. Contractile function was normal by echocardiography in awake mice, but the smaller heart and a slower heart rate reduced cardiac output. alpha(1)-AR stimulation did not activate extracellular signal-regulated kinase (Erk) and downstream kinases in ABKO myocytes, and basal Erk activity was lower in the intact ABKO heart. In female ABKO mice, heart size was normal, even after ovariectomy. Male ABKO mice had reduced exercise capacity and increased mortality with pressure overload. Thus, alpha(1)-ARs in male mice are required for the physiological hypertrophy of normal postnatal cardiac development and for an adaptive response to cardiac stress.

/pdf/the-a1a-c-and-a1b-adrenergic-receptors-are-required-for-3e2emces44.pdf

The α1A/C- and α1B-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse

Hypotension, Autonomic Failure, and Cardiac Hypertrophy in Transgenic Mice Overexpressing the α1B-Adrenergic Receptor

The purpose of this pretest-posttest experimental study was to determine if participating in six reminiscence therapy sessions would increase family coping strategies of individuals with chronic re...

James D. Thomas

Papers

Hypotension, Autonomic Failure, and Cardiac Hypertrophy in Transgenic Mice Overexpressing the α1B-Adrenergic Receptor

The Effect of Reminiscence Therapy on Family Coping