Subtypes of tachykinin receptors on tonic and phasic neurones in coeliac ganglion of the guinea-pig.
1. Intracellular recording techniques were used to investigate the characteristics of tachykinin receptors and their subtypes in tonic and phasic neurones, which constituted two major neuronal populations in the coeliac ganglion of the guinea-pig. 2. In 95% of phasic neurones a long-lasting after-hyperpolarization (LAH), 5-8 s in duration and 10-20 mV in amplitude, was observed following action potentials evoked by passing a train of depolarizing current pulses into the neurones. In contrast, LAH was observed in only 4% of tonic neurones. 3. In most tonic neurones, substance P (SP), neurokinin A (NKA) and senktide induced depolarizations, whereas in phasic neurones they usually inhibited LAH but rarely induced depolarization. 4. Tonic and phasic neurones were further classified into three groups based on their responses (depolarization for tonic neurones and LAH inhibition for phasic neurones) to these tachykinin receptor agonists: (1) neurones responsive to SP, NKA and senktide (71-78%); (2) those responsive to senktide but not to SP and NKA (12-23%) and (3) those not responsive to any of the three agonists (7-11%). 5. GR71251 (5 microM), an NK1-selective tachykinin receptor antagonist, depressed the depolarization in tonic neurones and the LAH inhibition in phasic neurones induced by SP and NKA, but not those induced by senktide. 6. Selective NK2 receptor agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, were without effect in both tonic and phasic neurones. Furthermore, an NK2 receptor antagonist, L659,877, did not inhibit the depolarization induced by NKA, SP or senktide in tonic neurones. 7. It is suggested that NK1 and NK3 receptors are present on a large proportion of coeliac ganglion neurones. In tonic neurones both subtypes of tachykinin receptors are coupled to membrane depolarization,whereas in phasic neurones activation of these receptors leads to inhibition of LAH. The present study also suggests that NKA evokes the depolarization in tonic neurones and the LAH inhibition in phasic neurones via NK1, but not NK2 receptors.
Zhao
F Y
FY
Department of Pharmacology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Saito
K
K
Yoshioka
K
K
Guo
J Z
JZ
Murakoshi
T
T
Konishi
S
S
Otsuka
M
M
D000818:Animals; D005260:Female; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D018039:Receptors, Tachykinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000145:classification*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D010446:Peptide Fragments; D018039:Receptors, Tachykinin; C054724:senktide; C076254:GR 71251; D013373:Substance P; D015288:Neurokinin A