Endothelins and rat carotid body: autoradiographic and functional pharmacological studies.
The effects of ET-1 and ET-3 on ventilation and carotid chemosensory discharge have been studied in rats anaesthetised with pentotarbitone. Autoradiographic studies were also performed in vitro to investigate the binding of [125I]ET-1 to rat carotid body, nodose ganglion and brain stem. ET-1 caused a dose-related hyperventilation that was abolished by cutting both carotid sinus nerves. Recordings of chemosensory discharge from the carotid sinus nerve confirmed that ET-1 caused chemoexcitation. ET-3 had only slight effects. The hyperventilation evoked by ET-1 was antagonised by the ETA receptor antagonist FR139317, but responses to hypoxia (10% oxygen) and to cyanide were unaffected. [125I]ET-1 bound to the carotid body, the nodose ganglion and to the brain stem, particularly in the region of the nucleus tractus solitarii. ET-1 binding in the carotid body was displaceable by FR139317, which is consistent with the functional evidence for ETA receptors in the carotid body. The effects of ET-1 on ventilation, coupled with the presence of ET binding sites in areas involved in respiratory and cardiovascular regulation, is consistent with a physiological role for ET in the control of respiration, but our evidence suggests that ET is not crucial for chemotransduction in acute hypoxia.
McQueen
D S
DS
Department of Pharmacology, University of Edinburgh Medical School, UK.
Dashwood
M R
MR
Cobb
V J
VJ
Bond
S M
SM
Marr
C G
CG
Spyer
K M
KM
D000818:Animals; D001345:Autoradiography; D001381:Azepines / Q000494:pharmacology; D002344:Carotid Body / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D003486:Cyanides / Q000633:toxicity; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015656:Respiratory Mechanics / Q000187:drug effects
D001381:Azepines; D003486:Cyanides; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D007457:Iodine Radioisotopes; C079574:FR 139317