Cysteinyl leukotriene receptor 2 is spatiotemporally involved in neuron injury, astrocytosis and microgliosis after focal cerebral ischemia in rats.

Cysteinyl leukotrienes (CysLTs), potent inflammatory mediators, are released from ischemic brain, and may regulate ischemic injury through activating CysLT1 and CysLT2 receptors. The CysLT1 receptor is closely associated with ischemic injury and post-ischemic repair; however, the CysLT2 receptor-mediated responses remain unknown. Here, we investigated the spatiotemporal profiles and implications of CysLT2 receptor expression and localization in rat brain after focal cerebral ischemia. CysLT2 receptors were normally localized in astrocytes in the cortex and around the ventricles. After focal cerebral ischemia, CysLT2 receptor expression was up-regulated in concert with neuronal and glial responses. In the acute phase (6-24 h), up-regulated CysLT2 receptors were restricted to injured neurons in the ischemic core; while in the late phase (3-28 days), the up-regulation was restricted to hypertrophic microglia (ischemic core) and mainly localized in hypertrophic astrocytes (boundary zone). Thus, the spatiotemporal profiles of CysLT2 receptor expression suggest that it plays regulatory roles in acute neuron injury, and astrocytosis and microgliosis in the late phase.

[Releases of bradykinin and substance P by heating hind paw of rat].

Contribution of kallikrein-kinin system to heat-induced substance P (SP) release into the periphery was studied by using plasma kininogens-deficient strain Brown Norway Katholiek (B/N-Ka) and normal strain Brown Norway Kitasato (B/N-Ki) rats. Bradykinin (BK) and SP levels in the sc perfusates of the hind instep were measured by radioimmunoassay. In B/N-Ki rat, immersion of hind paw into hot water (47 degrees C) for 20 min led to an increase of BK (43 +/- s 34 fmol.min-1) and SP (11.1 +/- 9.7 fmol.min-1) in the perfusate, whereas those in B/N-Ka rat (BK 1.3 +/- 1.0 fmol.min-1 (P < 0.01), SP 5.5 +/- 3.5 fmol.min-1 (P < 0.05)) were remarkably less. Heat-induced extravasation (leakage of Evans blue) in B/N-Ka rat was also less than that in B/N-Ki rat (P < 0.05). Results suggest that kallikrein-kinin system is involved in the release of SP into the periphery, ie, BK released into the extravascular space by noxious heat stimulation intervenes in SP release.

[Effect of a leukotriene antagonist, ONO-1078, on electric stimulation of vagus (ESV)-induced bronchoconstriction and microvascular leakage in guinea pigs].

In atropine-pretreated guinea pigs, electric stimulation of vagus (ESV, 10 Hz, 5 ms, 2 V or 10 V, for 90 s) increased intrapulmonary pressure (IPP), and Evans blue extravasation in trachea, main bronchi, peripheral and distal intrapulmonary airways in a voltage-dependent manner. ONO-1078, a noval leukotriene antagonist, (0.03 and 0.1 mg.kg-1, iv) showed no remarkable inhibiting effect on ESV-induced increase of IPP. However, the agent significantly inhibited ESV-induced increase of Evans blue extravasation in the airways, especially in lower potency of stimulation (2 V). The results suggest that leukotrienes may be involved in airway microvascular leakage in response to neurogenic inflammation.

Effect of morphine on changes in cutaneous blood flow induced by antidromic stimulation of primary afferent fibers in the hind instep of rats.

The effects of morphine on the release of immunoreactive substance P (iSP) into the subcutaneous perfusate and the changes in cutaneous blood flow (CBF) elicited by antidromic stimulation of sectioned sciatic nerve were investigated in the instep of the hind paw of rats. Antidromic stimulation of the sectioned sciatic nerve induced a marked increase in iSP release into the subcutaneous perfusate and a biphasic flow response consisting of an initial transient decrease followed by an increase. Both the iSP release and the increase of the CBF evoked by antidromic stimulation (the second phase) were significantly inhibited by intra-arterial (i.a.) infusion of morphine (30 mumol/kg). These inhibitory effects of morphine were antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The i.a. infusion of SP (0.25 mumol/kg) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. Neither phase induced by i.a. infusion of SP was affected by preinfusion of morphine (10 or 30 mumol/kg, i.a.). We suggest that morphine applied locally mainly acts on the peripheral endings of small-diameter afferent fibers, not on blood vessels, and that activation of this site is involved in the regulation of the microcirculatory hemodynamics of cutaneous tissue through inhibition of SP release.