Plasma protein extravasation induced by mammalian tachykinins in rat skin: influence of anaesthetic agents and an acetylcholine antagonist

Abstract

1 The effect of mammalian tachykinins on plasma protein extravasation was assessed in the rat dorsal skin. Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) increased vascular permeability in a dose-related manner with a threshold dose of about 0.07 pmol in sodium pentobarbitone-anaesthetized animals. 2 Plasma protein extravasation induced by the tachykinins was 100-500 times less in magnitude in animals anaesthetized with urethane. 3 Plasma protein extravasation induced by SP (66 pmol) was significantly reduced (63%; P <0.001) by atropine (a muscarinic inhibitor) while that induced by NKA or NKB was unaffected by the inhibitor suggesting that a cholinergic component might only be involved in the vascular permeability elicited by SP. 4 The rank order of potency for the tachykinins on plasma protein extravasation was: NKB > SP> NKA (in absence of atropine) and NKB > NKA > SP (in presence of atropine), suggesting that this vascular response is mediated by a SP-E-receptor type.

Recombinant Neutral Endopeptidase Attenuates Substance P-Induced Plasma Extravasation in the Guinea Pig Skin

“…Be cause selective Hi and H2 histamine receptor antago nists, alone or in combination, did not affect the re sponses, the incomplete inhibition was not due to effects of histamine possibly released from mast cells by substance P [5,[29][30][31], This finding is consistent with previous studies showing that guinea pig mast cells, unlike human and rat mast cells, are refractory to stimulation by substance P [32,33]. Furthermore, because atropine had no effect, substance P-induced responses were not mediated by cholinergic musca rinic neurotransmission [28,34],…”

“…To determine whether substance P-induced plasma extravasation is mediated in part by cholinergic muscarinic neurotransmission [28], we injected substance P, 2.5 x I0~8 M, in the absence (control) or 15 min after injecting atro pine (10 '5 M, 50 pi) intradermally. Fig.…”

Effect of Substance P and Sar⁹Met(O₂)¹¹-Substance P on Cutaneous Capillary Permeability in Guinea Pig Skin

“…These data are in accordance with those obtained by Couture and Kerouac [20] in rats after subcutaneous injection of SP. It should be noted that when SP is administered intravenously, atropine does not modify its effect [ 15].…”

Perisphincteric Injection of Botulinum Toxin Type A

“…It is known that the release of SP from nociceptive peripheral nerve endings can cause a neural inflammation [35]. The microcirculation within the muscle can be changed by the vasodilatating effects of calcitonin gene–related peptide [36]and the increased vascular permeability effects of substance P, neurokinin A and B [37]. Thus, a whole chain of events in the peripheral muscle [38], once triggered, can contribute to the development of a deleterious muscle pathophysiology.…”