Endothelin modulates dihydropyridine receptor decreased binding in hippocampal slices from normotensive and spontaneously hypertensive rats.
Previous studies in rats have demonstrated both the link between voltage-operated calcium channels and endothelin and their cerebral involvement in the pathophysiology of spontaneous hypertension. In the present study, the interaction of endothelin with specific dihydropyridine (DHP) binding sites was investigated using the brain slices model. In rat hippocampal slices, pre-incubation with Bay K 8644 decreased [3H] (+) PN 200-110 binding. There was no difference in agonist-induced decrease of DHP binding in normotensive and spontaneously hypertensive (SH) rats. The effect of Bay K 8644 was partially inhibited by endothelin but not by angiotensin in both normotensive and hypertensive rats. These data compared to those of other studies suggest that DHP binding sites which are regulated by endothelin are post-synaptic. We conclude that brain slices provide a good in vitro model to study DHP receptor regulation and to explore endothelin interactions with DHP-sensitive Ca2+ channels.
Huguet
F
F
Institut des Xénobiotiques, Faculté de Médecine et de Pharmacie, Poitiers, France.
Brisac
A M
AM
Dubar
M
M
Ingrand
P
P
Piriou
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D016232:Endothelins / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D017275:Isradipine / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D016232:Endothelins; D009124:Muscle Proteins; D000804:Angiotensin II; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D017275:Isradipine