Antagonistic oxytocin/alpha2-adrenoreceptor interactions in the nucleus tractus solitarii: relevance for central cardiovascular control.
The modulation of the central cardiovascular effects of alpha2-adrenoceptor activation by oxytocin in the nucleus tractus solitarii has been evaluated by cardiovascular analysis and by quantitative receptor autoradiography. Microinjections in the nucleus tractus solitarii of a threshold dose of oxytocin effectively and significantly counteracted the vasodepressor and bradycardic actions of an ED50 dose of the alpha2-adrenoceptor agonist clonidine. The coinjection of a threshold dose of oxytocin with a threshold dose of clonidine did not produce any changes in the mean arterial pressure but a tachycardic response was observed. Receptor autoradiographical experiments showed that oxytocin (3 nM) significantly increased the Kd and Bmax values of [3H]p-aminoclonidine binding sites in the nucleus tractus solitarii compatible with a possible antagonistic interaction with the alpha2-adrenoceptors, and this effect was blocked by the presence of the specific oxytocin receptor antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin. These findings suggest the existence of an antagonistic oxytocin/alpha2-adrenoceptor interaction in nucleus tractus solitarii that may be of relevance for the demonstrated modulation of alpha2-adrenoceptor induced cardiovascular responses by oxytocin.
Díaz-Cabiale
Z
Z
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. zaida.diaz@neuro.ki.se
Narváez
J A
JA
Garrido
R
R
Petersson
M
M
Uvnäs-Moberg
K
K
Fuxe
K
K
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D010121:Oxytocin / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D017552:Solitary Nucleus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D014316:Tritium; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D006727:Hormone Antagonists; D018341:Receptors, Adrenergic, alpha-2; C047046:atosiban; D014316:Tritium; D010121:Oxytocin; C016986:apraclonidine; D003000:Clonidine; D014668:Vasotocin