The dihydropyridines modulate neurotensin inotropic action paradoxically.
The interaction of neurotensin and calcium channel modulators is examined in isolated electrically driven guinea pig left atrial appendages. Left guinea pig atria exposed to diltiazem become desensitised to neurotensin. There is no significant influence of verapamil pretreatment on the neurotensin inotropic action. Nifedipine pretreatment causes increase in the inotropic response of guinea pig atria to neurotensin. The regression line of neurotensin after pretreatment with nifedipine compared to the regression line of neurotensin alone has higher slope and is shifted to the left. The ED50 of neurotensin after nifedipine pretreatment compared with the ED50 of neurotensin alone results in potency ratio of 2.24. Bay K8644 significantly decreases the inotropic effect of ED100 of neurotensin. Results suggest that: (1) the mechanism of interaction of calcium channel modulators and neurotensin in the atrium does not depend on the calcium influx through calcium channel nor does it on the calcium channel itself; (2) the interaction of nifedipine and neurotensin is possibly dependent on dihydropyridine receptors, (3) the dihydropyridine binding site, possibly different from voltage-sensitive calcium channel, is somehow involved in the neurotensin action in guinea pig atria.
Golba
K S
KS
Department of Clinical Pharmacology, Silesian Academy of Medicine, Katowice, Poland.
Deja
M
M
Imiołek
P
P
Kotyla
P J
PJ
Biernat
J
J
Woś
S
S
Herman
Z S
ZS
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009496:Neurotensin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D009496:Neurotensin