FR 190997, a new kinin B2 receptor agonist of non-peptide nature, has been studied in three isolated vessels: the human umbilical vein (hUV), the rabbit jugular vein (rbJV), and the pig coronary artery (pCA). Bradykinin (BK) contracts the hUV and rbJV through smooth muscle B2 receptors, while it relaxes the pCA through endothelial receptors of the B2 type. Contractions of the hUV and rbJV in response to FR 190997 show slow onset and are not reproducible compared to the rapid and reproducible effect of BK. They reach only 70% and 30% of the BK-induced maximal contractions in the hUV and rbJV, respectively. The effects of FR 190997 are antagonised by HOE 140 and this antagonist shows similar pK(B) values against BK and FR 190997, indicating that the non-peptide agent interacts with the kinin B2 receptor. FR 190997 is inactive as relaxant of the pCA; in this tissue, it acts as a pure and competitive antagonist, with a pK(B) value of 7.6, while HOE 140 acts as an insurmountable antagonist (pK(B) 9.3). When tested as an antagonist, FR 190997 inhibits also the contractile effects of BK in the hUV (pK(B) 7.8) and in the rbJV (pK(B) 7.6). FR 190997 is selective for the B2 receptor since it does not interact with the B1, and is specific since it does not affect the contraction evoked by 5-hydroxytryptamine, endothelin-1, and noradrenaline in the hUV, or the relaxation induced by substance P in the pCA. FR 190997 shows therefore different pharmacological profiles in various preparations, acting as a partial agonist in the hUV and especially in the rbJV and as a pure antagonist in the pCA. This new compound could be of interest in understanding how non-peptide agonists may activate receptors for peptides.
Pharmacological characterisation of the first non-peptide bradykinin B2 receptor agonist FR 190997: An in vitro study on human, rabbit and pig vascular B2 receptors
RIZZI, Anna;CALO', Girolamo;VARANI, Katia;
1999
Abstract
FR 190997, a new kinin B2 receptor agonist of non-peptide nature, has been studied in three isolated vessels: the human umbilical vein (hUV), the rabbit jugular vein (rbJV), and the pig coronary artery (pCA). Bradykinin (BK) contracts the hUV and rbJV through smooth muscle B2 receptors, while it relaxes the pCA through endothelial receptors of the B2 type. Contractions of the hUV and rbJV in response to FR 190997 show slow onset and are not reproducible compared to the rapid and reproducible effect of BK. They reach only 70% and 30% of the BK-induced maximal contractions in the hUV and rbJV, respectively. The effects of FR 190997 are antagonised by HOE 140 and this antagonist shows similar pK(B) values against BK and FR 190997, indicating that the non-peptide agent interacts with the kinin B2 receptor. FR 190997 is inactive as relaxant of the pCA; in this tissue, it acts as a pure and competitive antagonist, with a pK(B) value of 7.6, while HOE 140 acts as an insurmountable antagonist (pK(B) 9.3). When tested as an antagonist, FR 190997 inhibits also the contractile effects of BK in the hUV (pK(B) 7.8) and in the rbJV (pK(B) 7.6). FR 190997 is selective for the B2 receptor since it does not interact with the B1, and is specific since it does not affect the contraction evoked by 5-hydroxytryptamine, endothelin-1, and noradrenaline in the hUV, or the relaxation induced by substance P in the pCA. FR 190997 shows therefore different pharmacological profiles in various preparations, acting as a partial agonist in the hUV and especially in the rbJV and as a pure antagonist in the pCA. This new compound could be of interest in understanding how non-peptide agonists may activate receptors for peptides.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
