R 56865 differentiates between contractile agents with respect to the nifedipine-sensitive component in the isolated rat aorta.
The interaction of the benzothiazolamine R 56865 with the nifedipine-sensitive component of the serotonin (5-HT)-, angiotensin II (AII)- and arginine-vasopressin (AVP)-induced contractions was studied in the isolated rat aorta. Nifedipine caused concentration-dependently (10(-9)-10(-6) mol/l) a slight rightward shift accompanied by a limited depression of the maximum of the concentration-response curves for 5-HT-, AII- and AVP-induced contractions. R 56865 (10(-5) mol/l) antagonized the contraction elicited by 5-HT and AII in a similar manner as nifedipine. The effect of R 56865 on 5-HT- and AII-induced contractions was no longer observed after pretreatment with nifedipine. The AVP-induced contraction was not affected by R 56865 (10(-5) mol/l). As shown previously, R 56865 is a weak inhibitor of potential-operated channels but inactive on Ca2+ channels activated by NA. In conclusion, R 56865 does not only differentiate between depolarization and receptor-stimulation, but also between the activation of Ca2+ channels by different types of receptors. We propose that R 56865 may interact with Ca2+ channels at a site which plays a role in their activation.
Koch
P
P
Janssen Research Foundation, Neuss, FRG.
Wilhelm
D
D
Wilffert
B
B
Peters
T
T
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001127:Arginine Vasopressin / Q000494:pharmacology; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D052160:Benzothiazoles; D015220:Calcium Channels; D010880:Piperidines; D013844:Thiazoles; D000804:Angiotensin II; D001127:Arginine Vasopressin; D012701:Serotonin; C054551:R 56865; D009543:Nifedipine; D002118:Calcium