Characterization of NK₁ and NK₂ tachykinin receptors in guinea‐pig and rat bronchopulmonary and vascular systems

Abstract

1 NK1 and NK2 tachykinin receptors were characterized in guinea-pig and rat bronchopulmonary systems and in the vasculature of the rat by use of radioligand binding and/or functional studies.2 The radioligands for NKI and NK2 receptors ([3H]-SP and [3H]-pNKA, respectively) did not label tachykinin receptors in homogenates of rat lungs or bronchi. In contrast, in the guinea-pig, [3H]-SP bound with high affinity to these tissues (KD = 0.23 ± 0.08 nM and 0.34 ± 0.05 nM, for lungs and bronchi, respectively). The total number of binding sites was 4.6 fold greater in bronchus (B,,,, = 135 ± 27 fmol mg-1 protein) than in lung homogenates (B,,,,, = 5 These studies indicate that NKI and NK2 receptors are both present in the guinea-pig bronchopulmonary system whereas only NK1 receptors are detectable in the rat vasculature under our experimental conditions. Furthermore, NKI receptors in the guinea-pig bronchopulmonary system are pharmacologically distinct from those present in the rat vascular system, since both agonist potencies and antagonist affinities differ between the two species.

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK1 receptors and TXA2

“…Whether EDC and EDR are mediated by the same NK1 receptor remains to be clarified. NK1 receptors in the guinea-pig bronchopulmonary system and rat vascular system are different pharmacologically (Floch et al, 1994). We have found that unlike EDC, naturally occurring tachykinins all cause EDR according to the rank order of potency SP > NKA > NKB (unpublished data).…”

“…The presence offunctional NK1 receptors on the endothelium has been demonstrated in human umbilical arteries (Greeno et al, 1993). The tachykinin receptor mediating EDR is also the NK1 subtype in guinea-pig and rabbit pulmonary arteries (Emonds-Alt et al, 1993;Floch et al, 1994). Whether EDC and EDR are mediated by the same NK1 receptor remains to be clarified.…”

Temporal increase in the reactivity of pulmonary vasculature to substance P in chronically hypoxic rats

“…However, the dose of SP needed to produce a marked increase in P pa was much larger than that required in the isolated guinea pig lung (20) or the isolated rabbit pulmonary arterial strip (23). This difference might be due mainly to fewer NK 1 receptors in the rat lung than in the guinea pig lung (8). In addition, there might be a difference in NK 1 receptors between the rat and the guinea pig lungs (8).…”

“…This difference might be due mainly to fewer NK 1 receptors in the rat lung than in the guinea pig lung (8). In addition, there might be a difference in NK 1 receptors between the rat and the guinea pig lungs (8).…”

Regional heterogeneity of substance P-induced endothelium-dependent contraction, relaxation, and -independent contraction in rabbit pulmonary arteries

“…SP causes endothelium-dependent relaxation (EDR) through the production of nitric oxide (NO) via NK 1 receptors in pre-contracted guinea-pig and rabbit pulmonary arteries (D'Orleans-Juste et al, 1986;Emonds-Alt et al, 1993;Floch et al, 1994) and endothelium-independent contraction (EIC) via NK 2 receptors in non-contracted rabbit pulmonary arteries (D'Orleans-Juste et al, 1986). We have reported that SP causes endothelium-dependent contraction (EDC) via NK 1 receptors and the production of TXA 2 at low concentrations and EIC via NK 2 receptors at higher concentrations in the distal portion of rabbit intrapulmonary arteries (Shirahase et al, 1995).…”