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|Title:||Actions of D-amino acid-substituted analogues of des-Asp-angiotensin I on the central pressor action of angiotensin III|
|Keywords:||angiotensin analog, D-amino acid substituted|
|Citation:||Radhakrishnan, R., Sim, M.K. (1995). Actions of D-amino acid-substituted analogues of des-Asp-angiotensin I on the central pressor action of angiotensin III. European Journal of Pharmacology 294 (1) : 337-339. ScholarBank@NUS Repository. https://doi.org/10.1016/0014-2999(95)00686-9|
|Abstract:||The ability of intracerebroventricularly (i.c.v.) administered D-amino acid-substituted analogues of des-Asp-angiotensin I to attenuate the central pressor action of angiotensin III in the rat was investigated. Of the 9 D-amino acid-substituted analogues, only D-tyrosine-des-Asp-angiotensin I was active. I.c.v. D-tyrosine-angiotensin I but not i.c.v. D-isoleucine-angiotensin I (when prevented from degradation by angiotensin converting enzyme with captopril) also attenuated the central pressor action of angiotensin III. In vitro incubation of angiotensin I, D-tyrosine-angiotensin I and D-isoleucine-angiotensin I with brain homogenate resulted in the formation of des-Asp-angiotensin I, D-tyrosine-des-Asp-angiotensin I and D-isoleucine-des-Asp-angiotensin I, respectively. This shows that i.c.v. angiotensin I and D-tyrosine-angiotensin I were converted by brain aminopeptidase to des-Asp-angiotensin I and D-tyrosine-des-Asp-angiotensin I, respectively, which then attenuated the pressor action of angiotensin III. When compared to the findings of similar D-substitution studies carried out with angiotensin II and [Sar1,Ile8]angiotensin II by other investigators, des-Asp-angiotensin I has a stringent structural-activity relationship. These findings suggest that, at the physiological level, des-Asp-angiotensin I is formed from angiotensin I and that the nonapeptide probably acts on a distinct subtype of angiotensin receptors.|
|Source Title:||European Journal of Pharmacology|
|Appears in Collections:||Staff Publications|
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