By the sequential administration of alpha 1- and alpha 2-blockers it can be shown, in the pithed rabbit, that the dose/pressor response curve to noradrenaline consists of two separate curves, one for each receptor. alpha 2-mediated responses predominate at low doses and alpha 1-mediated responses predominate at high doses. Pressor responses to sympathetic nerve stimulation have, similarly, an alpha 2 component at low frequencies and a dominant alpha 1-mediated response at high frequencies: a residual response is resistant to combined alpha 1- plus alpha 2-blockade. This alpha-blocker-resistant pressor nerve response was further analysed in the pithed rat and was found to be partly susceptible to alpha,beta-methylene ATP, which desensitizes purinergic responses. However, reserpine pretreatment produced a greater reduction of nerve-mediated pressor responses than did alpha-blockade, suggesting that part of the 'alpha-blocker resistant' response might be adrenergic. It is concluded that sympathetic vasopressor nerve transmission is mediated for the greater part by alpha 1- and alpha 2-adrenoceptors but that there is evidence for contributions from non-alpha-adrenergic and 'purinergic' elements. An even greater proportion of the responses to circulating catecholamines is attributable to the alpha-receptors with a relatively small but significant 'resistant' component.

Adenosine Triphosphate↗

PubMed1985

Analysis of the alpha-adrenoceptor-mediated, and other, components in the sympathetic vasopressor responses of the pithed rat.

The vascular receptors activated following sympatho-adrenal stimulation were determined by analysing the effects of 'selective' antagonists on the vasopressor response to spinal sympathetic nerve activation in the pithed rat. The net vascular response to adrenal stimulation was a balance between alpha-adrenoceptor-mediated vasoconstriction and beta-adrenoceptor-mediated vasodepression. Part of the alpha-adrenoceptor-mediated response was 'prazosin-sensitive' (alpha 1) and the remainder was abolished by rauwolscine (alpha 2). As with adrenal stimulation, direct sympathetic nerve stimulation of the vasculature evoked pressor responses which were partly resistant to prazosin. Rauwolscine only partly blocked the prazosin-sensitive component. Reserpine pretreatment led to smaller responses than prazosin plus rauwolscine. Thus, the response resistant to alpha-adrenoceptor antagonists could be mediated, in part, by adrenoceptors distinct from alpha-adrenoceptors, as currently defined. alpha, beta-Methylene ATP reduced the nerve-mediated pressor response after alpha-adrenoceptor blockade or reserpine pretreatment but not in drug-free controls. The results suggest that stimulation of the adrenal medulla can produce a vasopressor response which consists of summating alpha 1- and alpha 2-adrenoceptor-mediated components, and is identical to the effect of injected adrenaline. In contrast, the response to vasopressor nerve stimulation appears to be essentially mediated by alpha 1-adrenoceptors, with a facilitatory influence from alpha 2-adrenoceptors. A further response obtained after alpha-adrenoceptor blockade may contain a purinergic component and another which is adrenergic but not mediated by stimulation of alpha-adrenoceptors.

Adenosine Triphosphate↗

PubMed1975

Central objective is to understand patient's experience.

Explore the source record for details and available documents.

Curriculum↗

PubMedDate not supplied

Multiple synthesis by the multipin method as a methodological tool.

The multipin method of peptide synthesis is demonstrated as a potent methodological tool, where large numbers of comparative studies can be performed concurrently. Two studies are presented. In each study, the test peptides were simultaneously synthesized, and the products examined by high throughput ion spray mass spectrometry and reverse-phase HPLC. In the first study, comprising 24 experiments, peptides 1 (AELFSTHYLAFKEDYSQ-NH2) and 2 (LKDFRVYFREGRDQLWKGPG-NH2) were prepared using Fmoc-Axx/BOP/HOBt/NMM [100 : 100 : 100 : 150 mM) and Fmoc-AXX/HATU/HOAt/NMM (100 : 100 : 100 : 150 nM) with 60, 90 and 120 min coupling times. The two reagent combinations were found to give comparable results. The second study compared the N-terminal coupling of Fmoc-Asn-OH, Fmoc-Asn(Mbh)-OH, Fmoc-Asn(Mtt)-OH, Fmoc-Asn(Tmob)-OH and Fmoc-Asn(Trt)-OH in the synthesis of seven test peptides: 3, NVQAAIDYIG-cyclo(KP): 4. NTVQAAIDYIG-cyclo(KP): 5. NRVYVHPFNL: 6. NRVYVHPFHL: 7. NEAYVHDAPVRSLN: 8. NQLVVPSEGLYLIYSQVLFK; 9, NPNANPNANPNA. A total of 33 experiments were performed. Peptides 3 and 4 were selected to highlight the effect of steric bulk of each Asn derivative on coupling efficiency. Reagent efficiency, as measured by target peptide purity, was as follows: Fmoc-Asn(Tmob)-OH > Fmoc-Asn-OH > Fmoc-Asn(Mtt)-OH = Fmoc-Asn(Trt)-OH > Fmoc-Asn(Mbh)-OH.

Amino Acid Sequence↗

PubMedDate not supplied

Persistent electrocardiographic changes after flecainide overdose.

Flecainide acetate is a potent class 1C antiarrhythmic agent, overdosage with which is rare. An overdose is reported in a patient on long-term therapy, resulting in life-threatening arrhythmias and prolonged electrocardiographic abnormalities.

Adolescent↗