Bradykinin, desArg(9)BK, some agonist analogues and several antagonist
s have been tested in isolated organs in order to identify bradykinin
B-2 receptor subtypes. The initial pharmacological characterization wa
s made in the rabbit jugular vein and the guinea pig ileum, two widely
used B-2 preparations which have shown marked differences in their se
nsitivities to both agonists and antagonists. The study has then been
extended to peripheral tissues (stomach, colon, urinary bladder) of fo
ur species (the rat, guinea pig, rabbit and man) and to isolated vesse
ls (rabbit jugular vein, rabbit vena cava, guinea pig pulmonary artery
, rat portal vein) in order to determine if pharmacologic receptor sub
types may be related to species. It has been shown that B-2 receptors
in rat and guinea pig tissues belong to a similar pharmacological enti
ty, a receptor which is different from that mediating the responses of
rabbit and human tissues. Agonists order of potency ([Hyp(3)]BK > BK
> [Aib(7)]BK) obtained in the rabbit jugular vein is different from th
at found in the guinea pig ileum (BK less than or equal to [Aib(7)]BK
> [Hyp(3)]BK). Affinities of competitive antagonists (for instance DAr
g[Hyp(3),DPhe(7),Leu(8)]BK) in rabbit tissues are higher than in guine
a pig and rat tissues by at least 2 log units, while the non peptidic
compound WIN 64338 is more active (also by two log units) in guinea pi
g than in human and rabbit tissues. The non competitive long-acting an
tagonist HOE 140 is very potent and equally active in the four species
. Some antagonists (peptides without unnatural residues, peptides with
unnatural residues, non peptides) have been shown to be specific for
kinin receptors and selective for the B-2. Altogether, the present res
ults a) confirm the existence of two B-2 receptor subtypes, b) suggest
that receptor subtypes may be species dependent and c) indicate that
the B-2 receptor subtype found in the rabbit is similar to that found
in man.