Effect of ryodipine on electromechanical parameters of heart and vessels, cAMP phosphodiesterase activity and swelling-contraction cycle of mitochondria.
2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1,4 -dihydropyridine (ryodipine, PP-1466), an effective Ca2+ channel blocker, diminishes contraction force and decreases duration of action potential in the frog heart ventricle strips. Dissociation constants K0.5 are 2 x 10(-7), 5 x 10(-7), and 10(-6) mol/l for PP-1466, nifedipine and nicardipine, respectively (at 0.25-0.3 Hz stimulation). One molecule of PP-1466 or nifedipine apparently interacts with two receptors on the channel (n = 0.5), nicardipine with one receptor (n = 1). The binding energy of PP-1466 and nifedipine increases at closed and diminishes at open channels which is in contrast to nicardipine, whose effect is irreversible. Thus, the site of nicardipine action differs from that of PP-1466 and nifedipine. PP-1466 (10(-8) mol/l--10(-6) mol/l) suppresses contraction force and diminishes frequency of spontaneous contractions of the rabbit atria, and also displays antagonism to the effect of Ca2+ upon rabbit auricle contractions. In the isolated rabbit aorta and portal vein PP-1466 is more antagonistic to contractions caused by Ca2+ than by epinephrine. Both competitive and non-competitive types of antagonism can be distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)
Velena
A H
AH
Dubur
G J
GJ
Vitolina
R O
RO
Kimenis
A A
AA
Selga
M J
MJ
Zarinsh
G V
GV
Narusevicius
E V
EV
Macianskiene
R A
RA
Gendvilienè
V I
VI
Simkhovich
B Z
BZ
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D001001:Anura; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology; D002417:Cattle; D004095:Dihydropyridines; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents; D004095:Dihydropyridines; D011725:Pyridines; C038806:1,4-dihydropyridine; D009529:Nicardipine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D009543:Nifedipine; C045912:ryodipine