The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep.

The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of -56.4% (52.3-60.5%, 95% confidence interval) and for lys-bradykinin -52.8% (46.5-59.1%). The ED50 values were 0.69 (0.51-1.32) and 1.46 (1.19-2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses (greater than 1.9 pmoles) of both kinins. Intravenous indomethacin (5 mg.kg-1) increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4 microns at 0.35 ml.min-1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.

Kallidin-induced stimulation of inositol phosphate production and prolactin release in rat anterior pituitary cells.

The effect of the kinin, kallidin (lysyl-bradykinin) on phosphoinositide metabolism and prolactin secretion was examined in male rat anterior pituitary cells in primary culture. Kallidin was found to stimulate both total inositol phosphate production and prolactin release. The stimulation of inositol phosphate was biphasic in nature, similar to that previously reported for bradykinin, although kallidin was approximately 10-fold more potent. Kallidin also stimulated prolactin secretion provoking a maximal stimulation of 193.0 +/- 11.1 (sem)% at 1 mumol/l. These findings suggest that kallidin-induced prolactin secretion may be mediated intracellularly by activation of phosphoinositide metabolism. The B2 receptor antagonists had no significant inhibitory effects on kallidin-stimulated phosphoinositide metabolism or prolactin release. The B1 agonist des-Arg9-bradykinin has previously been shown to have no effect on either parameter. As the effects of kinins on anterior pituitary cells do not appear to be mediated by either of the known kinin receptors, they may, therefore, act via a hitherto unrecognised kinin receptor.

Blockade of kinin-induced responses of the guinea-pig isolated urinary bladder by the extract of Mandevilla velutina.

1. The crude extract (CE) from M. velutina (0.2-0.8 mg/ml), antagonized in a dose-dependent and reversible manner bradykinin (BK)- and lysyl-BK-induced contractions of the guinea-pig urinary bladder in vitro. 2. Schild plots yielded nominal pA2 values (as g/ml) of 3.5 and 3.7, but the slopes were significantly greater than unity. 3. At concentrations 2-10-fold higher, the CE failed to affect responses to acetylcholine or histamine. 4. In electrically-stimulated tissue, BK, L-BK and M-L-BK potentiated nerve-mediated twitch responses and increased muscular tone. The B1 agonist [des-Arg9]-BK, was inactive up to 10 microM. 5. The CE from M. velutina (0.4 mg/ml) inhibited both actions of the kinins.

[Antagonism of parmidin to kinin effects]. / Izuchenie antagonizma parmidina k éffektam kininov.

Parmidin in 10(-9)-10(-5) g/ml concentrations displays specific and competitive antagonism to spasmogenic effects of bradykinin and methionyl-lysil-bradykinin on isolated segments of the guinea pig ileum, rat uteral cornua, cat jejunum and spiral strips of the rabbit aorta. Its antagonism to the spasmogenic effect of lysil-bradykinin is of both competitive and non-competitive character. In rats parmidin in 100 mg/kg dose decreased the paw edema, induced by kinins but it did not influence the similar effect of histamine and that of prostaglandin F2.

Role of calcium ions in kinin-induced chloride secretion.

Electrogenic ion transport across the epithelium lining the descending colon of male Sprague-Dawley rats has been measured under short-circuit conditions. Responses to kallidin (lysylbradykinin) were inhibited by 70% if calcium was removed from the solution bathing the basolateral aspect of the tissue. Under identical conditions responses to prostaglandin E1 and dibutyryl cyclic adenosine monophosphate were not changed. Forskolin, which directly activates the catalytic subunit of adenylate cyclase, was inhibited by 35% by calcium removal, whereas responses to the phosphodiesterase inhibitor isobutylmethylxanthine were inhibited by 45% by the same procedure. In the absence of calcium, strontium could substitute in promoting the chloride secretory events triggered by kallidin. Magnesium ions antagonized the effects of the kinin in the presence of calcium ions in the bathing solution. The effects of kallidin were partially antagonized by verapamil and trifluoperazine and were potentiated by isobutylmethylxanthine. These results, together with earlier evidence, suggest that kinin elicits a chloride secretory response in this epithelium by stimulating the formation of prostaglandins which then activate adenylate cyclase. Extracellular calcium ions appear to have an important role in the proximal part of this cascade for prostaglandin generation. However, biochemical correlates of these biophysical responses presented in the following paper indicate a more complex role for calcium in the genesis of the kinin response.