Autoradiographic evidence for a bradykinin/angiotensin II receptor-receptor interaction in the rat brain.
Using angiotensin II (ANG II) to compete with (3-[125I]iodotyrosyl-4, Sar1, Ile8)ANG-II ([125I]Sar1, Ile8)ANG II) for its binding sites in the nucleus of the solitary tract (nTS) and the paraventricular hypothalamic nucleus (PV) bradykinin (10 nM) reduced the IC50 value (48 nM) of ANG II, an action blocked by the bradykinin B2 antagonist HOE-140 (100 nM). In contrast, when analysing the high-affinity site (Kd 3.1 nM) for [125I]ANG II in the nTS bradykinin (10 nM) increased the Kd value. Thus, a central bradykinin/ANG II receptor interaction may exist involving a differential regulation of the high- and low-affinity ANG II receptors in the nTS. This regulation by bradykinin of angiotensin receptors in the nTS may help to explain the central vasopressor effect of bradykinin.
Fior
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DR
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Hedlund
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PB
Fuxe
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D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000502:physiology*; D007457:Iodine Radioisotopes; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects
D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D000804:Angiotensin II; C065679:icatibant; D012504:Saralasin; D001920:Bradykinin