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1
Content available remote

Function of nociceptin and opioid OP4 receptors in the regulation of the cardiovascular system

100%
Malinowska B., Godlewski G., Schlicker E.
Journal of Physiology and Pharmacology
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2002
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tom 53
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nr 3
Nociceptin is the endogenous ligand of the opioid OP4 or ORL1 (opioid receptor-like1) receptor. It decreases blood pressure and heart rate in anesthetized and conscious rats and mice after its intravenous and intracerebroventricular injection in a manner sensitive to OP4 but not to OP1-3 (or , and µ opioid) receptor antagonists. OP4 receptors involved in the cardiovascular effects of nociceptin were identified on sensory afferent fibres, in brain areas including the nucleus tractus solitarii and the rostral ventrolateral medulla, on preganglionic and/or postganglionic sympathetic and parasympathetic nerve fibres innervating blood vessels and heart or directly on these target organs. These receptors do not seem to be tonically activated but may play a role in the pathophysiology of inflammation, arterial hypertension and cardiac or brain circulatory ischemia.
2
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Histamine H3 receptors - general characterization and their function in the cardiovascular system

100%
Malinowska B., Godlewski G., Schlicker E.
Journal of Physiology and Pharmacology
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1998
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tom 49
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nr 2
3
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Identification of a presynaptic cannabinoid CB1 receptor in the guinea-pig atrium and sequencing of the guinea-pig CB1 receptor

100%
Kurz C. M., Gottschalk C., Schlicker E., Kathmann M.
Journal of Physiology and Pharmacology
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2008
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tom 59
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nr 1
We studied whether cannabinoid CB1 receptors occur on the sympathetic neurones innervating the guinea-pig atrium and renal cortex. Atrial and cortical kidney pieces preincubated with [3H]-noradrenaline were superfused and the electrically (3 Hz)-evoked tritium overflow was examined. The evoked overflow in atrium was inhibited by the cannabinoid agonist WIN 55,212-2 maximally by 35%; its concentration-response curve was shifted to the right by the CB1 antagonist rimonabant (pA2 8.3), which, by itself, did not affect the evoked overflow. The evoked overflow in the renal cortex was not altered by WIN 55,212-2. The muscarinic agonist oxotremorine and prostaglandin E2 inhibited the evoked overflow maximally by 55 and 65% in atrium and by 80 and 55% in kidney, respectively. Furthermore, the nucleotide sequence of the guinea-pig CB1 receptor was determined (GenBank DQ355990). The deduced amino acid sequence has a high homology to the corresponding sequence of man (98.7%) and rat or mouse (99.2%). In conclusion, presynaptic CB1 receptors leading to inhibition of noradrenaline release occur in guinea-pig atrium but not renal cortex. The deduced amino acid sequence of the guinea-pig CB1 receptor shows a homology of 99% to the CB1 receptor sequence of rodents and humans.
4
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Role of endocannabinoids in cardiovascular shock

88%
Malinowska B., Lupinski S., Godlewski G., Baranowska U., Schlicker E.
Journal of Physiology and Pharmacology. Supplement
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2008
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tom 59
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nr 8
5
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Potential involvement of a propranolol-insensitive atypical beta-adrenoceptor in the vasodilator effect of cyanopindolol in the human pulmonary artery

88%
Kozlowska H., Schlicker E., Kozlowski M., Baranowska M., Malinowska B.
Journal of Physiology and Pharmacology
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2006
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tom 57
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nr 3
The aim of our study was to examine whether non ß1-/ß2-adrenoceptors participate in the relaxation of the human pulmonary artery. For this purpose the vasodilatory effect of the non-conventional partial ß-adrenoceptor agonist cyanopindolol was examined. Cyanopindolol (1 - 300 µM), studied in the presence of the ß1-/ß2-adrenoceptor antagonist propranolol, relaxed the human pulmonary artery preconstricted with serotonin 1 µM in a concentration-dependent manner (maximally by about 80%). This effect was diminished by bupranolol 10 µM (an antagonist of ß1-ß3-adrenoceptors and the low affinity state of the ß1-adrenoceptor) and CGP 20712 10 µM (known to antagonize the low-affinity state of the ß1-adrenoceptor at high concentrations). In further experiments, the effect of ß-adrenoceptor ligands on the serotonin-induced vasoconstriction was examined. The concentration-response curve for serotonin was not affected by cyanopindolol 30 µM, bupranolol 10 µM and CGP 20712 10 µM but shifted to the right by cyanopindolol 100 and 300 µM; the serotonin 5-HT2A receptor antagonist ketanserin 0.3 µM abolished the maximum contraction elicited by serotonin. In conclusion, the present study reveals that the vasodilatory effect of cyanopindolol in the human pulmonary artery consists of two components, i.e. activation of a propranolol-insensitive atypical ß-adrenoceptor and antagonism against 5-HT2A receptors.
6
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Bi-directional CB1 receptor-mediated cardiovascular effects of cannabinoids in anaesthetized rats: role of the paraventricular nucleus

76%
Grzeda E., Schlicker E., Luczaj W., Harasim E., Baranowska-Kuczko M., Malinowska B.
Journal of Physiology and Pharmacology
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2015
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tom 66
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nr 3
7
Content available remote

Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors

64%
Zelaszczyk D., Kozlowska H., Baranowska U., Baranowska M., Reutelsterz A., Kiec-Kononowicz K., Malinowska B., Schlicker E.
Journal of Physiology and Pharmacology
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2009
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tom 60
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nr 1
51-60
Bupranolol is an antagonist at the cardiostimulatory low-affinity state of ß1-adrenoceptors and we were interested whether this effect is shared by its fluorine (GD-6), methyl (DZ-51) and isopropyl analogue (DZ-13) and by the analogue hydroxylated at the tertiary butyl moiety (DZ-52). (-)-Bupranolol and compounds (-)-GD-6, (+)-GD-6, (-)-DZ-13, (+)-DZ-13, DZ-51 and DZ-52 antagonized the CGP 12177-induced tachycardia in pithed rats with “apparent pA2 values” of 6.1, 6.1, 4.6, 5.5, 4.6, 5.1 and 5.3, respectively. For comparison, their potencies and affinities at the high-affinity state of ß1-adrenoceptors were determined, using the xamoterol-induced tachycardia in pithed rats and [3H]CGP 12177 binding to rat cerebrocortical membranes. The respective “apparent pA2 values” in the functional experiments were 7.9, 8.1, 5.4, 8.4, 5.7, 7.3 and 6.8 and the pKi values in the binding experiments were 8.8, 8.4, 6.9, 8.5, 6.7, 8.4 and 8.2. In conclusion, (-)-bupranolol and its fluorine analogue (-)-GD-6 are equipotent at the low-affinity state of ß1-adrenoceptors. The stereoselectivity of GD-6 and DZ-13 suggests that the low-affinity state is indeed a receptor.
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