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 functional and anti-ischaemic effects of the phosphodiesterase (PDE)-inhibitors, amrinone, milrinone and levosimendan, a new agent combining PDE-inhibitory with calcium-sensitizing properties, were investigated in rabbit isolated hearts (Langendorff, constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol l-1, 37 degrees C). Anti-ischaemic effects were studied in electrically-driven hearts (200 beats min-1). ⋯ It is concluded that amrinone and milrinone possess similar functional profiles in rabbit isolated hearts and a higher inotropic and chronotropic efficacy than levosimendan. At functionally equieffective concentrations, milrinone and levosimendan show similar anti-ischaemic effects, related to an improvement of myocardial perfusion. The calcium-sensitizing properties seem not to be relevant for cardioprotection by levosimendan at the concentration used.
-
1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli, and hyperalgesia as assessed by the hot plate test. We characterized prostaglandin E receptor subtypes (EP1-3) involved in these sensory disorders by use of 7 synthetic prostanoid analogues. 2. ⋯ MB28767 (EP3)showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg-S5 Microg kg-1. Butaprost(EP2) induced hyperalgesia at doses higher than 50 ng kg-1.5. These results demonstrate that PGE2 may exert allodynia through the EP1-receptor and hyperalgesia through EP2- and EP3-receptors in the mouse spinal cord.
-
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.