Presynaptic dopamine receptors mediate the inhibitory action of dopamine agonists on stimulation-evoked pressor responses in the rat.
The effects of the dopamine agonists TL-99, M-7 (N, N-dimethyl analogues of aminotetralins) and N, N-dinpropyldopamine (NNPD) on stimulation-evoked pressor responses and tachycardia in pithed Sprague-Dawley rats were investigated when pressor responses to the compounds per se had subsided. Various antagonists were used to characterise the effects of the dopamine agonists. 2 M-7 (3 micrograms/kg i.v.), and NNPD (1 mg/kg i.v.), but not TL-99 (1-30 micrograms/kg i.v.), inhibited pressor responses evoked by low frequency electrical stimulation of the spinal cord in the pithed rat. 3 M-7 (3 micrograms/kg i.v.), but neither NNPD (1 mg/kg i.v.) nor TL-99 (1-30 micrograms/kg), inhibited tachycardia evoked by low frequency electrical stimulation of the spinal cord in the pithed rat. 4 The inhibition of stimulation-evoked pressor responses by M-7 and NNPD was prevented by pimozide, metoclopramide and sulpiride but not by yohimibine, atropine, cimetidine or propranolol. 5 The inhibition of stimulation-evoked tachycardia by M-7 was prevented by yohimbine (and to a certain extent by sulpiride) but not pimozide, metoclopramide, atropine or cimetidine. 6 Pressor responses elicited by TL-99, M-7 and NNPD were selective antagonised by yohimbine, but not by prazosin, indicating that these responses were mediated by stimulation of vascular postsynaptic alpha 2-adrenoreceptors. 7 This study demonstrates that, in the rat, presynaptic dopamine receptors exist on sympathetic pre- or postganglionic nerve endings to blood vessels, but not on sympathetic pre- or postganglionic nerve endings to the heart, where inhibition by M-7 of stimulation-evoked tachycardia is mediated by stimulation of presynaptic alpha 2-adrenoreceptors.
D000818:Animals; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009281:Naphthalenes / Q000037:antagonists & inhibitors*; D009284:Naphthols / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors*
D009281:Naphthalenes; D009284:Naphthols; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C009957:5,6-dihydroxy-2-dimethylaminotetralin; C020895:N,N-di-n-propyldopamine; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; D004298:Dopamine