Use of Selective Agonists and Antagonists to Characterize Tachykinin Receptors Mediating Airway Responsiveness in Anaesthetized Guinea-pigs
✍ Scribed by L. Yuan; E. Burcher; B.S. Nail
- Publisher
- Elsevier
- Year
- 1994
- Tongue
- English
- Weight
- 426 KB
- Volume
- 7
- Category
- Article
- ISSN
- 0952-0600
No coin nor oath required. For personal study only.
✦ Synopsis
SUMMARY: Tachykinins are potent bronchoconstrictors. Here we have used novel highly selective agonists and antagonists to characterize tachykinin receptors mediating bronchoconstriction and hypotension in anaesthetized, paralysed guinea-pigs. Total lung resistance (\left(R_{L}\right)) and dynamic lung compliance (\left(C_{\mathrm{dp}}\right)) were measured using an online, breath-by-breath method to analyse lung mechanics. The effects of iv injections of neuropeptide (\gamma(\mathrm{NP} \gamma)), (\left[\mathrm{Sar}^{9}, \mathrm{Met}\left(\mathrm{O}{2}\right)^{11}\right.) ]-SP (Sar-SP) (NK-1 agonist), [Lys (\left.{ }^{5}, \mathrm{MeLeu}^{9}, \mathrm{Nle}^{10}\right])-NKA(4-10) (Lys-NKA) (NK-2 agonist) and senktide (NK-3 agonist) were compared, before and after iv injection of the NK-1 antagonist CP 96345 or the NK-2 antagonists MDL 29913 and SR 48968. NP (\gamma), Sar-SP and Lys-NKA, but not senktide, increased (R{L}) and decreased (C_{\mathrm{d}, \mathrm{p}}), accompanied by a fall in blood pressure (BP). The potency for increase of (R_{L}) was Lys(\mathrm{NKA}>\mathrm{NP} \gamma \simeq) Sar-SP, for reduction of (C_{\mathrm{dyn}}) was Lys-NKA (=) Sar-SP>NP (\gamma), and for fall in BP was SarSP>NP (\gamma>>) Lys-NKA. CP 96345 ( (50 \mathrm{nmol} / \mathrm{kg} & 200 \mathrm{nmo} / \mathrm{kg}) ) significantly antagonized the changes in (R_{L}, C_{\mathrm{d} g \mathrm{n}}) and BP induced by Sar-SP, and the fall in BP (but not changes in lung mechanics) in response to NP (\gamma), but did not alter any responses to Lys-NKA. In contrast, MDL (29913(200 \mathrm{nmo} / \mathrm{kg} & 10 \mu \mathrm{mol} / \mathrm{kg})) weakly and SR 48968 ( (100 \mathrm{nmol} / \mathrm{kg}) ) potently inhibited the effects on (R_{L}) and (C_{\mathrm{dyn}}) induced by Lys-NKA and NP (\gamma). Our results show that both NK-1 and NK-2 receptors are represented in guinea-pig airways. MDL 29913 is a weak NK-2 antagonist in guinea-pig airways compared to SR 48968. In addition, NK-1 but not NK-2 receptors appear to be important in mediating the hypotensive response to these tachykinins. In spite of its ability to cause a fall in BP via NK-1 receptors, (\mathrm{NP} \gamma) exerted its effects on (R_{L}) and (C_{\mathrm{dya}}) solely via NK-2 receptors.