THE DIHYDROPIRIDINES MODULATE NEUROTENSIN INOTROPIC ACTION PARADOXICALLY

The interaction of neurotensin and calcium channel modulators is exami ned in isolated electrically driven guinea pig left atrial appendages. Left guinea pig atria exposed to diltiazem become desensitised to neu rotensin. There is no significant influence of verapamil pretreatment on the neurotensin inotropic action. Nifedipine pretreament causes inc rease in the inotropic response of guinea pig atria to neurotensin. Th e regression line of neurotensin after pretreatment with nifedipine co mpared to the regression line of neurotensin alone has higher slope an d is shifted to the left. The ED(50) of neurotensin after nifedipine p retreatment compared with the ED(50) of neurotensin alone resultes in potency ratio of 2.24. Bay K8544 significantly decreases the inotropic effect of ED(100) of neurotensin. Results suggest that: (1) the mecha nism of interaction of calcium channel modulators and neurotensin in t he atrium does not depend on the calcium influx through calcium channe l nor does it on the calcium channel itself; (2) the interaction of ni fedipine and neurotensin is possibly dependent on dihydropiridine rece ptors, (3) the dihydropiridine binding site, possibly different from v oltage-sensitive calcium channel, is somehow involved in the neurotens in action in guinea pig atria.