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A Lochner

Publications and source records attributed to A Lochner.

132 records · Page 8Linked to original sources
PubMedDate not supplied

The many faces of H89: a review.

H89 is marketed as a selective and potent inhibitor of protein kinase A (PKA). Since its discovery, it has been used extensively for evaluation of the role of PKA in the heart, osteoblasts, hepatocytes, smooth muscle cells, neuronal tissue, epithelial cells, etc. Despite the frequent use of H89, its mode of specific inhibition of PKA is still not completely understood. It has also been shown that H89 inhibits at least 8 other kinases, while having a relatively large number of PKA-independent effects which may seriously compromise interpretation of data. Thus, while recognizing its kinase inhibiting properties, it is advised that H89 should not be used as the single source of evidence of PKA involvement. H-89 should be used in conjunction with other PKA inhibitors, such as Rp-cAMPS or PKA analogs.

Animals↗
PubMedDate not supplied

Opioid receptor stimulation acts as mediator of protection in ischaemic preconditioning.

Involvement of the opioid receptors in preconditioning-induced protection has recently been described. The aims of this study were to establish whether: (i) opioid receptor stimulation acts as a trigger ( during the preconditioning protocol) or as a mediator ( during sustained ischaemia) of cardioprotection using either morphine or [D-ala(2), D-leu(5)] enkephalin (DADLE), a synthetic delta-opioid receptor agonist; ( ii) the beneficial effects of DADLE are protein kinase C ( PKC) -mediated; and (iii) inhibitory 'cross-talk' occurs between the beta-adrenergic and phosphatidylinositol pathways activated by release of endogenous catecholamines and opioids respectively during sustained ischaemia. The isolated, perfused working rat heart, subjected to 25 minutes' global ischaemia and 30 minutes' reperfusion, was used as the experimental model. The results showed that delta-opioid receptor stimulation with DADLE (10(-8) M), when administered for 3 x 5 minutes, had no effect, while when given 10 minutes before sustained ischaemia the drug significantly improved functional recovery during reperfusion. This indicates that opioid receptor stimulation acts as a mediator rather than a trigger in the protection elicited. Morphine ( 3 x 10(-7)) when administered in the same manner was without effect. Opioid receptor stimulation caused a marked reduction in the beta -adrenergic response to isoproterenol, indicating inhibitory cross-talk between the phosphatidyl-inositol and beta-adrenergic signal transduction pathways. However, reduction of the beta-adrenergic response to ischaemia does not appear to be the mechanism of opioid-induced protection, as indicated by 3',5' -cyclic adenosine monophosphate (cAMP) levels at the end of 25 minutes' global ischaemia. Opioid receptor-mediated protection against ischaemic damage is PKC-dependent, since DADLE-induced protection could be abolished by the inhibitor chelerythrine.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Proposed mechanisms for the anabolic steroid-induced increase in myocardial susceptibility to ischaemia/reperfusion injury.

UNLABELLED: Androgenic anabolic steroids (AAS) are often used by athletes to enhance athletic performance but are strongly associated with detrimental cardiovascular effects including sudden cardiac death. HYPOTHESIS: AAS use increases myocardial susceptibility to ischaemia/reperfusion injury. METHODS: Rats were trained (swimming) with or without intramuscular injection of nandrolone laurate (0.375 mg/kg). Untrained rats with or without nandrolone served as controls. Hearts were mounted on the Langendorff perfusion apparatus and mechanical function was measured before and after 20-min normothermic global ischaemia. Myocardial tissue samples were collected for determination of tissue cyclic nucleotide and TNFalpha concentrations. RESULTS: Anabolic steroids decreased the rate pressure product (RPP) of the exercise-trained rat heart [34 582 +/- 1 778 mmHg/min vs 28 868 +/- 2 446 mmHg/min for exercise-trained steroid-treated hearts (p < 0.05)]. Reperfusion RPP was lower in both the sedentary, and the exercise-trained, steroid-treated hearts than in their concurrent vehicle-treated controls (18 276 +/- 2 026 mmHg/min vs 12 018 +/- 1 725 mmHg/min for sedentary steroid-treated hearts and, 21 892 +/- 2 912 mmHg vs 12 838 +/- 1 536 mmHg/min for exercise-trained steroid-treated hearts). Myocardial TNFalpha [267.75 +/- 44.25 pg/g vs 190.00 +/- 15.75 pg/g (p < 0.05)] and cAMP concentrations [406.04 +/- 18.41 pmol/g vs 235.6 +/- 43.26 pmol/g (p < 0.05)] were elevated in the steroid-treated hearts when compared with their untreated counterparts. CONCLUSIONS: Supraphysiological doses of anabolic steroids, whether taken during exercise training or under sedentary conditions increase myocardial susceptibility to ischaemia/reperfusion injury in our model. This increased susceptibility may be related to steroid-induced increases in the pre-ischaemic myocardial cAMP concentrations and/or increases in both pre-ischaemic and reperfusion TNFalpha concentrations.

Anabolic Agents↗
PubMedDate not supplied

Melatonin prevents cardioprotection induced by a multi-cycle ischaemic preconditioning protocol in the isolated perfused rat heart.

The powerful cardioprotective actions of melatonin, the chief secretory product of the pineal gland, have been attributed largely to its free radical-scavenging properties. Free radicals play an important role in the triggering action of ischaemic preconditioning, the phenomenon whereby exposure of the heart to one or more short episodes of ischaemia leads to protection against a subsequent long period of ischaemia. The aim of this study was, therefore, to establish whether melatonin, in view of its free radical-scavenging ability, would affect the beneficial actions of preconditioning. Isolated, perfused, working hearts were subjected to 1 x 5 minute or 3 x 5 min ischaemic preconditioning protocols, in the presence or absence of melatonin (50 microM), followed by 20 minutes global ischaemia and 30 minutes reperfusion. Use was also made of sodium nitroprusside (100 microM), a nitric oxide (NO) donor and preconditioning mimetic. Using functional recovery as the endpoint, melatonin abolished the cardioprotective effects of a multi-cycle (3 x 5 min) preconditioning protocol, while having no effect on a one-cycle (1 x 5 min) protocol or SNP (1 x 5 or 3 x 5 min) preconditioning. The results suggest that free radicals play an important role in the cardioprotection induced by a multi-cycle ischaemic preconditioning protocol and that this process could be attenuated by a potent scavenger such as melatonin.

Animals↗