Abstract
Responses of gastric myenteric neurones evoked by the mammalian tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were investigated using conventional intracellular recording methods. Application of the tachykinins caused a long lasting depolarization of the membrane potential which was associated with increased spike discharge and augmented excitability of the cells. The responses slowly desensitized. Additionally, cross desensitization occurred between SP, NKA and NKB. Both the NK-1 receptor agonist [Sar9,MetO2 11]SP and the NK-2 receptor agonist [β-Ala8]NKA(4–10) had no effect on the electrical properties of the neurones. Only the NK-3 receptor agonist [MePhe7]NKB mimicked the excitatory response observed during SP, NKA and NKB applications. [MePhe7]NKB-induced desensitization abolished the response to SP, NKA and NKB. However, long lasting applications of [Sar9,MetO2 11]SP or [β-Ala8]NKA(4–10) had no effect on the SP, NKA or NKB responses. The excitatory effect of SP, NKA and NKB remained unchanged during application of the tachykinin analogues [D-Arg1, d-Trp7,9,Leu11]SP and [Tyr5,d-Trp6,8,9,Arg10]NKA(4–10). The results indicate that SP, NKA and NKB act as excitatory neuromodulators within the enteric nervous system of the stomach. The effects of SP, NKA and NKB appeared to be mediated by activation of NK-3 receptors.
Similar content being viewed by others
References
Allescher H-D, Kostolanska F, Tougas G, Fox JET, Regoli D, Drapeau G, Daniel EE (1989) The actions of neurokinins and substance P in canine pylorus, antrum and duodenum. Peptides 10:671–679
Barber WD, Burks TF (1987) Tachykinins: local gastric effects and brain stem responses. Am J Physiol 252:G365-G373
Bartho L, Holzer P (1985) Search for a physiological role of substance P in gastrointestinal motility. Neuroscience 16:1–32
Delbro D, Fändricks L, Lisander B, Anderson SA (1981) Hexamethonium-resistant, atropin-sensitive vagal excitation of the feline stomach — activation of an unknown fibre system. Acta Physiol Scand 112:493–494
Delbro D, Fändriks L, Rosell S, Folkers K (1983) Inhibition of antidromically induced stimulation of gastric motility by substance P receptor blockade. Acta Physiol Scand 118:309–316
Galligan JJ, Tokimasa T, North RA (1987) Effects of three mammalian tachykinins on single enteric neurons. Neurosci Lett 82:167–171
Grundy D, Schemann M (1991) Neurology of the stomach. In: Gustavson S, Kumar D (eds) The stomach. Churchhill Livingston London (in press)
Guard S, Watson SP, Maggio JE, Too HP, Watling KJ (1990) Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes. Br J Pharmacol 99:767–773
Hanani M, Chorev M, Gilon C, Selinger Z (1988) The actions of receptor-selective substance P analogs on myenteric neurons: an electrophysiological investigation. Eur J Pharmacol 153:247–253
Holzer P (1989) Ascending enteric reflex: multiple neurotransmitter systems and interactions. Am J Physiol 256:G540-G545
Holzer-Petsche U, Schimek E, Amann R, Lembeck F (1985) In vivo and in vitro actions of mammalian tachykinins. Naunyn Schmiedebergs Arch Pharmacol 330:130–135
Holzer-Petsche U, Lembeck F, Seitz H (1987) Contractile effects of substance P and neurokinin A on rat stomach in vivo and in vitro. Br J Pharmacol 90:273–279
Jacoby HI (1988) Gastrointestinal tachykinin receptors. Life Sci 43:2203–2208
Katayama Y, North RA (1978) Does substance P mediate slow synaptic excitation within the myenteric plexus? Nature 274:387–388
Konishi S, Song S-Y, Ogawa T, Kanazawa I (1989) Tachykinins produce fast and slow depolarizations in sympathetic neurons of rat coeliac-superior mesenteric ganglia. Brain Res 490:162–165
Laufer R, Wormser U, Friedman Z, Gilon C, Chorev M (1985) Neurokinin B is a preferred agonist for a neural substance P receptor and its action is antagonized by enkephalin. Proc Natl Acad Sci USA 82:7444–7448
Maggi CA, Patachini R, Santicioli P, Giuliani S, Turini D, Barbanti G, Beneforti P, Misuri D, Meli A (1989) Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogeneous neuropeptides. Naunyn Schmiedebergs Arch Pharmacol 339:415–423
Maggi CA, Patacchini R, Giachetti A, Meli A (1990) Tachykinin receptors in the circular muscle of the guinea-pig ileum. Br J Pharmacol 101:996–1000
Mawe GM (1990) Intracellular recording from neurones of the guinea-pig gall-bladder. J Physiol (Lond) 429:323–338
Mawe GM, Schemann M, Wood JD, Gershon MD (1989) Immunocytochemical analysis of potential neurotransmitters present in the myenteric plexus and muscular layers of the corpus of the guinea pig stomach. Anat Rec 224:431–442
Murase K, Ryu PD, Randic M (1989) Tachykinins modulate multiple ionic conductances in voltage-clamped rat spinal dorsal horn neurons. J Neurophysiol 61:854–865
Nemeth PR, Ewart WR, Wood JD (1983) Effects of the putative substance P antagonists [D-Pro2,D-Phe7,D-Trp9] and [D-Pro2,D-Trp7,D-Trp9] on electrical activity of myenteric neurones. J Auton Nerv Sys 8:165–169
Neuhuber WL (1987) Sensory vagal innervation of the rat esophagus and cardia: a light and electron microscopic anterograde tracing study. J Auton Nerv Sys 20:243–255
Regoli D, Drapeau G, Dion S, Couture R (1988) New selective agonists for neurokinin receptors: pharmacological tools for receptor characterization. Trends Pharmacol Sci 9:290–295
Rovero P, Pestellini V, Maggi CA, Pataccini R, Regoli D, Giachetti A (1990) A highly selective NK-2 tachykinin receptor antagonist containing D-tryptophan. Eur J Pharmacol 175:113–115
Schemann M, Wood JD (1989) Electrical behaviour of myenteric neurones in the gastric corpus of the guinea-pig. J Physiol (Lond) 417:501–518
Smith TK, Furness JB (1988) Reflex changes in circular muscle activity elicited by stroking the mucosa: an electrophysiological analysis in the isolated guinea-pig ileum. J Auton Nerv Sys 25:205–218
Surprenant A, North RA, Katayama Y (1987) Observations on the actions of substance P and [D-Arg1,D-Pro2,D-Trp7,9,Leu11] substance P on single neurons of the guinea pig submucous plexus. Neuroscience 20:189–199
Tamura K, Wood JD (1989) Electrical and synaptic properties of myenteric plexus neurones in the terminal large intestine of the guinea-pig. J Physiol (Lond) 415:275–298
Too H-P, Cordova JL, Maggio JE (1989) A novel radioimmunoassay for neuromedin K. I. absence of neuromedin K-like immunoreactivity in guinea pig ileum and urinary bladder. II. Heterogeneity of tachykinins in guinea pig tissues. Regul Pept 26:93–105
Wade PR, Wood JD (1988) Actions of serotonin and substance P on myenteric neurons of guinea-pig distal colon. Eur J Pharmacol 148:1–8
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schemann, M., Kayser, H. Effects of tachykinins on myenteric neurones of the guinea-pig gastric corpus: involvement of NK-3 receptors. Pflügers Arch 419, 566–571 (1991). https://doi.org/10.1007/BF00370296
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00370296