Inactivation of Bradykinin in Rat Lung

Ryan, James W.; Roblero, J.; Stewart, John M.

doi:10.1007/978-1-4684-3198-8_32

Cited by 76 publications

(32 citation statements)

References 4 publications

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“…However, the product of aminopeptidase P action on this vasoactive peptide, des-Arg-bradykinin, is a good substrate for the dipeptidyl peptidase IV [13]. Though an immunocytochemical localization of aminopeptidase P on endothelial cells is lacking, we demonstrate here that bradykinin is an excellent substrate for the highly purified enzyme, whereas Lys-bradykinin (kallidin) is no substrate for aminopeptidase P, but converted to bradykinin by aminopeptidase N, another important activity of endothelial cells surfaces [28].…”

Section: Biological Significancementioning

confidence: 77%

“…However, there is now good evidence that the lung membrane-bound aminopeptidase P, together with angiotensin-converting enzyme, inactivates circulating bradykinin (see [27] for review). Namely, perfusion of rat lung with radiolabelled bradykinin yields Arg and ProPro dipeptide [28], a sequestration which can be attributed to the sequential action of aminopeptidase P and dipeptidyl peptidase IV and is mimiced with partly purified lung enzymes [13]. Since dipeptidyl peptidase IV does not cleave Pro-Pro bonds, bradykinin is resistant to this enzyme located in high concentrations at the vascular endothelium [29].…”

Section: Biological Significancementioning

confidence: 99%

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Aminopeptidase P from rat brain

Harbeck

Mentlein

1991

European Journal of Biochemistry

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Aminopeptidase P (EC 3.4.11.9) was purified from rat brain cytosol. A subunit Mr of 71000 was determined for the reduced, denaturated protein whereas an Mr of 143 000 was determined for the native enzyme. The purified aminopeptidase P selectively liberated all unblocked, preferentially basic or hydrophobic ultimate amino acids from di‐, tri‐ and oligopeptides with N‐terminal Xaa‐Pro‐ sequences. Corresponding peptides with penultimate Ala instead of Pro were cleaved with much lower rates; oligopeptides with residues other than Pro or Ala in the penultimate position appeared not to be substrates for the enzyme. Several bioactive peptides with Xaa‐Pro sequences, especially bradykinin, substance P, corticotropin‐like intermediate lobe peptide, casomorphin and [Tyr]melanostatin were shortened by the N‐terminal amino acid by aminopeptidase P action. Rat brain aminopeptidase P was optimally active at pH 7.6–8.0 in the presence of Mn2 +. Chelating agents and SH‐reacting reagents inhibited the enzyme, but common inhibitors of aminopeptidases, like amastatin or bestatin, of prolidase or of dipeptidyl peptidases II and IV, like N‐benzoyloxycarbonyl‐proline or ɛ‐benzyl‐oxycarbonyl‐lysyl‐proline, as well as antibiotics like β‐lactam ones, bacitracin or puromycin, had little or no effect.

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Section: Biological Significancementioning

confidence: 77%

Section: Biological Significancementioning

confidence: 99%

Aminopeptidase P from rat brain

Harbeck

Mentlein

1991

European Journal of Biochemistry

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“…A possible effect of bacitracin on the enzymatic degradation of B4310 would, however, need more detailed investigation. Bradykinin is largely eliminated from the blood by a single passage through the pulmonary circulation (Ferreira & Vane, 1967a,b;Ryan et al, 1970). Angiotensin converting enzyme seems to play a critical role in the inactivation of bradykinin (Dorer et al, 1974a,b), although other peptidases such as aminopeptidase P may be involved additionally in the lung (Orawski et al, 1987) and in the periphery (Marceau et al, 1981;Whalley, 1987).…”

Section: Agonistic and Antagonistic Propertiesmentioning

confidence: 99%

Effects of the bradykinin antagonist B4310 on smooth muscles and blood pressure in the rat, and its enzymatic degradation

Griesbacher

Lembeck

Saria

1989

British J Pharmacology

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Austria1 Six competitive bradykinin (Bk) antagonists were tested for their agonistic properties on the rat uterus. Five of these peptides showed agonistic effects only at concentrations at least two orders of magnitude higher than those of bradykinin. 2 The antagonistic potency of Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk (B4310) in the rat uterus (pA2 = 7.24) and in the rat duodenum (pA2 = 7.31) was very similar to that determined in an earlier study for the antagonism of the bradykinin-induced stimulation of the trigeminal nerve in the rabbit iris sphincter muscle preparation (pA2 = 7.59). 3 The fall in mean arterial blood pressure induced by i.a. injections of bradykinin was greatly reduced during an i.a. infusion of B4310, but not 10min thereafter, which indicates a rapid inactivation of B4310 in,vivo. Bacitracin possibly interferes with the enzymatic cleavage of B4310 but seems to have no effect on the degradation of bradykinin. 4 An i.a. infusion of captopril greatly enhanced the potency of bradykinin in inducing a fall in arterial blood pressure, confirming the important role of angiotensin converting enzyme in the cleavage of bradykinin. However, the design of this experiment did not allow conclusions about the effect of captopril on the degradation of B43 10. 5 B4310 incubated with rat lung tissue disappeared from the incubation medium within a few minutes, i.e. as fast as bradykinin, which explains its short duration of action in vivo. Captopril partially inhibited the cleavage of both bradykinin and B4310. 6 The present results show that the bradykinin antagonists available at present are useful tools for the investigation of the biological role of bradykinin. However, the susceptibility to enzymatic degradation may limit their usefulness in animal experiments or in clinical studies.

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“…This result implied a decrease in CE activity at di-oestrus which had not been observed with Al as substrate. Because bradykinin is a substrate for inactivating peptidases apart from CE (Ryan, Roblero & Stewart, 1970), an alternative explanation of changing bradykinin inactivation involves these non-CE bradykininases. An estimate of these non-CE bradykininases can be obtained by measuring the metabolism of /8-homo Pro7-bradykinin, a peptide which is not a substrate for CE (Ondetti & Engel, 1975).…”

Section: Pmentioning

confidence: 99%

Communications

1979

The Journal of Physiology

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It has been reported that changes of intrapulmonary CO2 in the dog alter ventilation, via the vagus nerve (Bartoli et al. 1974; Banzett et al. 1978). An attempt was made to quantitate this CO2 reflex through a range of intrapulmonary CO2 and airway pressure (Paw) levels.Dogs were anaesthetized with chloralose-urethane (initial dose 350 mg urethane, 110 mg chloralose per kg; continuous infusion of half that dose per hour) and paralysed with Flaxedil (7 mg/kg). The chest was opened and a blocking catheter was placed in the main bronchus of the left lung to allow independent but synchronous ventilation of both lungs by a dual-piston pump. The left lung was vascularly isolated by externally occluding the left pulmonary artery, adequate gas exchange was maintained by the right lung, which was vagally denervated. Thus, arterial blood gases could be held constant during experimental manoeuvres. Efferent activity from the C5 root of the phrenic nerve was recorded and integrated as described by Bartoli et al. (1975).In the vascularly isolated lung, various constant levels of CO2, between 1 and 8 %, were attained and the integrated phrenic signal recorded both during phasic changes in Pw at different end-expiratory loads (between 3 and 7 cm H20) and at different levels of static lung inflation (Paw between 4 and 16 cm H20).Both phasic and static lung inflation resulted in a rhythmic pattern of phrenic nerve activity. Alterations in end-expiratory load or in static Pw were reflected in changes of this pattern, the predominant effect with increasing lung pressure being a prolongation of TE (time from peak discharge to onset of the next phrenic burst).We did not detect any consistent influence of lung CO2 on the relationship between static Paw and phrenic nerve activity. With phasic lung inflation effects of CO2 on the integrated phrenic signal were only observed when lung CO2 was below 1-5 %. These effects were, however, invariably associated with changes in peak Paw Above 1-5 % CO2 changes were not observed in the integrated phrenic signal.The results indicate that a decrease in ventilatory drive may be induced only with reduction in CO2 to low levels and suggest that lung mechanics may play a significant role in the underlying mechanism.

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Inactivation of Bradykinin in Rat Lung

Cited by 76 publications

References 4 publications

Aminopeptidase P from rat brain

Aminopeptidase P from rat brain

Effects of the bradykinin antagonist B4310 on smooth muscles and blood pressure in the rat, and its enzymatic degradation

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