British journal of pharmacology
-
1. Electrophysiological recordings were made from presumed dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area of rat brain slices. The ability of selective dopamine receptor agonists to hyperpolarize neurones and inhibit cell firing, as well as the ability of dopamine receptor antagonists to block responses to quinpirole were compared. 2. ⋯ Ritanserin,a 5-HT2 receptor antagonist that also binds to D2.u. dopamine receptors, caused a slight but significant shift in the concentration-effect curve to quinpirole with an estimated pKA of 6.97 +/- 0.13(n =4) in the substantia nigra and pKA of 7.12 +/- 0.22 (n =4) in the ventral tegmental area.5. Comparison of these data with the binding affinity for cloned dopamine receptors demonstrates that the responses to quinpirole on dopaminergic neurones in both the A9 (substantia nigra) and A10(ventral tegmental area) brain areas are consistent with the activation of predominantly D2, and not D3 or D4 dopamine receptors. Furthermore, the similarity in functional affinity of antagonists for these receptors suggest that the mesolimbic selectivity of atypical neuroleptics, like clozapine, may be a consequence of their actions on other receptors or their effects elsewhere in the brain.
-
1. The effects of long-term atenolol (25 mg kg-1 day-1) therapy on arterial function were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The 14-week treatment attenuated the increase in blood pressure by approximately 30 mmHg in SHR, but did not affect blood pressure in WKY rats. 2. ⋯ In conclusion, the moderate antihypertensive effect of atenolol in SHR was accompanied by enhancement of beta-adrenoceptor-mediated and normalization of endothelium-dependent arterial relaxation. Furthermore, ability to sequester calcium into cellular stores, and function of Na+,K+-ATPase were augmented in vascular smooth muscle. Therefore, the present results suggest that the long-term blood pressure-lowering action of atenolol in this type of genetic hypertension is accompanied by improved arterial relaxation and normalization of endothelial function.
-
1. Collagenases are thought to play a major role in the pathology of gas gangrene caused by Clostridium histolyticum, because they can destroy the connective tissue barriers. We investigated possible mediators involved in the oedema formation and plasma protein extravasation which follow the injection of a collagenase (EC 3.4.24.3) from Clostridium histolyticum into one hind paw of anaesthetized rats. 2. ⋯ In conclusion, bradykinin appears to be the main mediator of inflammation induced by a collagenase from Clostridium histolyticum. As well as having direct relevance to a known pathological condition,collagenase-induced paw oedema could prove to be a useful model in inflammation research and in the investigation of bradykinin antagonists. The present results might provide an experimental basis for clinical investigations of the effects of icatibant in infectious diseases where the release of collagenases from bacteria causes rapid spreading of inflammation.
-
1. The effects of the sulphonylurea, glibenclamide (20 mg kg-1, i.v.), at a dose that blocks vascular potassium channels, on systemic and splanchnic haemodynamics (radioactive microspheres) were studied in conscious rats. 2. Glibenclamide significantly decreased cardiac index and hepatic artery blood flow while it significantly increased vascular resistance in systemic, portal and hepatic arterial territories. 3. ⋯ Another sulphonylurea, glipizide (20 mg kg-1, i.v.), induced significant systemic and splanchnic vasoconstriction. 7. Thus, the glibenclamide-induced blockade of vascular potassium channels caused a vasoconstriction in the systemic and splanchnic vascular beds. In these territories, therefore, the opening of glibenclamide-sensitive potassium channels might be responsible for a basal vasodilator tone.
-
Comparative Study
Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49.
1. S 16257 is a new bradycardic agent. Its electropharmacological profile has been compared to that of the known bradycardic compound UL-FS 49 (Zatebradine). ⋯ S 16257 (3 MicroM) induced only a weak prolongation of AP (+ 14.1 +/- 5.0% and + 14.8 +/- 3.3% for APD50 and APD90, respectively) significantly smaller than in the case of UL-FS 49.5. These results show that S 16257 slows the rate of spontaneous AP firing in isolated SAN mainly by a reduction of the diastolic depolarization of the cells, which suggests an inhibition of the pace-maker current (If). S 16257 and UL-FS 49 are equipotent in their bradycardic effect but S 16257 is more specific as it induces less increase in myocardial repolarization time.