Identification of pre- and postsynaptic bradykinin receptor sites in the vas deferens: evidence for different structural prerequisites.
The effect of bradykinin on the neuroeffector junction of the isolated rat vas deferens was studied in tissues stimulated transmurally at a frequency of 0.15 Hz. Bradykinin caused two distinct and independent actions: it potentiated the magnitude of the muscular response to the electrically driven twitches and, in addition, contracted the smooth muscle generating an increased muscular tone. The former action is referred to as the neurogenic or presynaptic effect, whereas the latter effect is called the musculotropic or postjunctional action. The neurogenic effect was abolished by tetrodotoxin or tissue denervation either by cold storage or chemical sympathectomy after 6-hydroxydopamine administration. However, these procedures did not significantly modify the musculotropic potency of bradykinin. Both actions of the peptide are receptor-mediated, as minor structural modifications in the amino acid sequence caused significant changes in biological potency. In addition, the peptide analog, [Thi5,8-D-Phe7]-bradykinin, behaved as an agonist at the presynaptic site but as an antagonist at the muscular site. The most potent peptide analog to produce the neurogenic effect was Met-Lys-bradykinin followed by Lys-bradykinin and [Tyr8]-bradykinin. In contrast, the potency of these peptide analogs acting at the postsynaptic site was about the same. des Arg9 bradykinin and des Arg9-[Leu8]-bradykinin were inactive at the pre- and postjunctional site. The neurogenic action of bradykinin was not mimicked by angiotensin II, neurotensin, substance P or vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003080:Cold Temperature; D003714:Denervation; D004745:Enkephalins / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009496:Neurotensin / Q000494:pharmacology; D009638:Norepinephrine / Q000032:analysis; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
D004745:Enkephalins; D006892:Hydroxydopamines; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D014667:Vasopressins; D009496:Neurotensin; D013779:Tetrodotoxin; D016627:Oxidopamine; D009638:Norepinephrine