Differences in neurokinin receptor pharmacology between rat and guinea‐pig superior cervical ganglia

Abstract

1 The depolarizations elicited by seven neurokinin receptor agonists were examined in both rat and guinea-pig superior cervical ganglia by use of grease-gap methodology in the presence of tetrodotoxin (0.1 pM). Responses were normalised with respect to 1 AM eledoisin.2 The rank order of agonist potency in the rat ganglia was senktide > substance P > substance P methyl ester = eledoisin = Sar-Met-substance P > neurokinin B > neurokinin A, whereas in guinea-pig superior cervical ganglion (SCG) the rank order was senktide > Sar-Met-substance P > neurokinin B = eledoisin = substance P methyl ester. The concentration-effect curves for substance P and neurokinin A in guinea-pig ganglia were biphasic which precluded the determination of meaningful potency values. 3 The maximal depolarization achieved by subtype selective ligands was different between these two species. On rat and guinea-pig SCG, the NK3-selective ligand, senktide, produced a maximal depolarization of 27% and 274% respectively, whereas the NK,-selective ligand, substance P methyl ester, produced depolarizations of 77% and 64% respectively. 4 The depolarizations induced by substance P methyl ester and senktide in either species were unaffected by atropine (1 pM), suggesting a lack of involvement of presynaptic neurokinin receptors in the generation of the response. 5 The potency of substance P methyl ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the peptidase inhibitors bacitracin (40pgmlm'), leupeptin (4fpgmhl'), and chymostatin (2 g ml-1). Similarly, these peptidase inhibitors had no effect on the maximal depolarizations achieved by any of these agonists. 6 It is evident that rat and guinea-pig superior cervical ganglia possess both NK, and NK3 receptors, but that their net contribution to depolarizations are different between the two species. The depolarizations in guinea-pig SCG are mediated predominantly by an NK3 subtype and in rat SCG by an NK, receptor subtype.

Electrophysiological effects of tachykinins and capsaicin on guinea‐pig bronchial parasympathetic ganglion neurones.

“…The NK-3 receptor subtype has been reported on neurones in the myenteric plexus (Yau, Bowen & Youther, 1991;Schemann & Keyser, 1991), superior cervical ganglion (Seabrook, Main, Bowery, Wood & Hill, 1992), and neostriatum (Arenas, Alberch, Perez-Navarro, Solsana & Marsal, 1991). In the rat neostriatiiii, (Arenas et al 1991) and guinea-pig myenteric plexus (Laufer, Wormser, Friedman, Gilon, Chorev & Selinger, 1985;Yau et al 1991), NK-3 receptor activation is associated with acetylcholine release.…”

Tachykinins as mediators of slow EPSPs in guinea‐pig gall‐bladder ganglia: involvement of neurokinin‐3 receptors.

“…Yau, Mandel, Dorsett & Youther (1992) have demonstrated NK-3-induced acetylcholine release in the guinea-pig myenteric plexus. In superior cervical ganglia of rat and guinea-pig, neurones were depolarized by the NK-3 receptor activators senktide and NKB (Seabrook, Main, Bowery, Wood & Hill, 1992). In many systems, activation of neurokinin receptors results in depolarization of neurones.…”

Bradykinin receptors in mouse and rat isolated superior cervical ganglia

“…The methods for dissecting and recording from isolated rodent superior cervical ganglia were the same as described by Seabrook et al (1992). Ganglia were obtained from male Sprague-Dawley rats (150 to 250 g), or from male C57 mice (40 to 60 weeks old), which were then desheathed and placed in a grease-gap recording chamber.…”