Effects of the CCK(A) receptor antagonists SR 27897B and PD140548 on baroreflex function in conscious rats.
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| Abstract |
Since the cardiovascular effects of cholecystokinin (CCK) seem to particularly involve the A ('peripheral') subtype of CCK (CCK[A]) receptor, we examined the actions of two novel, highly selective CCK(A) receptor antagonists, PD140548 (N-alpha-methyl-N[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbony l]-L-tryptophyl]-D-3-(phenylmethyl)-beta-alanine) and SR 27897B (1-[[2-(4-(2-chlorophenyl)thiazol-2-yl)aminocarbonyl]acetic acid) on CCK-induced alterations in blood pressure and heart rate, and on the baroreceptor reflex in the conscious, instrumented rat. CCK (2 microg, i.v.) produced a pressor response and biphasic effects on heart rate involving an initial bradycardia followed by a pronounced tachycardia. Administration of PD140548 (10 mg/kg, i.v.) and SR 27897B (0.6 mg/kg, i.v.) significantly inhibited the pressor effects of CCK (35 and 47%, respectively), whilst reversing the bradycardic responses to a tachycardia. The CCK(A) receptor antagonists had different effects on the baroreceptor heart rate reflex since only PD140548 caused a significant increase in the gain or sensitivity of the reflex. This effect of PD140548 on gain is likely to occur via a central mechanism and may reflect the increased lipophilicity of PD140548 relative to SR 27897B. Overall, these investigations provide new evidence for the involvement of the CCK(A) receptor in cardiovascular regulation.
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| Authors | M W Bunting, P M Beart, R E Widdop |
| Journal | European journal of pharmacology (Eur J Pharmacol) Vol. 337 Issue 1 Pg. 35-9 (Oct 15 1997) ISSN: 0014-2999 [Print] Netherlands |
| PMID | 9389378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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