The role of the opioid-like receptor 1 (ORL1) and its endogenous ligand, nociceptin/orphanin FQ (N/OFQ), in nociception, anxiety, and learning remains to be defined. To allow the rapid identification of agonists and antagonists, a reporter gene assay has been established in which the ORL1 receptor is functionally linked to the cyclic AMP-dependent expression of luciferase. N/OFQ and N/OFQ(1-13)NH(2) inhibited the forskolin-induced luciferase gene expression with IC(50) values of 0.81 +/- 0.5 and 0.87 +/- 0.16 nM, respectively. Buprenorphine was identified as a full agonist at the ORL1 receptor with an IC(50) value of 8.4 +/- 2.8 nM. Fentanyl and 7-benzylidenenaltrexone displayed a weak agonistic activity. The ORL1 antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ((1-13))NH(2) clearly behaved as an agonist in this assay with an IC(50) value of 85 +/- 47 nM. Thus, there is still a need for antagonistic tool compounds that might help to elucidate the neurophysiological role of N/OFQ.

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Conventional active stress tests for the evaluation of coronary artery disease are not feasible for patients in whom a significant blood pressure increase during a stress procedure should be avoided, for example, those with a coexisting aortic aneurysm. Transesophageal echocardiography (TEE) with simultaneous atrial pacing is a new, highly specific, and sensitive stress technique for the detection of coronary artery disease. Furthermore, TEE can be performed safely with only mild blood pressure increases. Therefore in the present case report of a 70-year-old male, application of combined TEE and atrial pacing was used successfully to exclude the hemodynamic significance of a circumflex artery stenosis and avoided a significant blood pressure increase before surgical correction of an abdominal aortic aneurysm.

In hypertensives, a reduced coronary flow reserve is observed and may contribute to angina pectoris and silent (painless) myocardial ischemia, which frequently occur in these patients even in the absence of coronary artery disease (CAD). To assess the frequency of ischemia-type ST-segment depressions in these patients and the influence of heart rate (HR) and blood pressure (BP) as major determinants of myocardial oxygen demand and to test the effects of beta-blocker therapy (10-20 mg betaxolol/day for 4 weeks) on these variables, simultaneous 24-h Holter and 24-h ambulatory BP monitoring was performed in 19 patients with hypertension (age, 43-71 years; nine women, 10 men) without CAD (stenosis < 50% in angiography). Before treatment, 25 periods of significant ST-segment depressions with a total duration of 470 min were observed in nine patients. ST-segment depressions were significantly correlated with preceding increases in HR and the rate-pressure product. The majority (79%) of episodes with ST-segment depression were clinically painless. In this open study, beta-blockade significantly decreased the number of episodes with ST-segment depressions to six in four of 15 patients and the total duration to 38 min (p < 0.05). The data demonstrate that HR seems to be associated with the development of ischemic ST-segment deviations in patients with hypertension without CAD. Antihypertensive therapy in these patients should target not only sufficient BP control, but also reduction of ischemic events.