Fast and slow depolarizations produced by substance P and other tachykinins in sympathetic neurons of rat prevertebral ganglia.
Using intracellular recording, we examined the effects of three mammalian tachykinins, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), on sympathetic neurons of isolated rat coeliac-superior mesenteric ganglia (C-SMG). The 3 tachykinins elicited two distinct depolarizing responses in ganglion cells: fast depolarization with time-to-peak of 1-2 sec and duration of 5-10 sec, and slow depolarization with time-to-peak of about 20 sec and duration of 120-140 sec. Both fast and slow responses persisted in a solution containing low Ca2+ and high Mg2+ or tetrodotoxin, which indicates that the tachykinins directly act on ganglion cells to produce fast and slow depolarizations. The two types of tachykinin-induced responses exhibited clearly distinguishable properties. The membrane conductance was increased during the fast response, but not significantly changed, slightly decreased or sometimes increased during the slow response. Within certain range of membrane potential, the amplitude of fast response increased upon membrane hyperpolarization and decreased upon depolarization of ganglion cells. In contrast, the amplitude of slow response associated with membrane conductance decrease was increased with membrane depolarization and decreased with hyperpolarization. The fast response was markedly suppressed in a Na(+)-deficient solution, a solution containing nominally zero Ca2+ (plus 0.1 mM EGTA in some cases), and in a solution containing Cd2+ or Mn2+, whereas the slow response was not affected in these solutions and was augmented in some cells in K(+)-free solution. Thus it seems that the increase in Ca(2+)-dependent cationic conductance underlies the fast response and that the slow response is produced at least in part by suppression of certain K+ channels. The fast response progressively decreased in amplitude upon repeated application of the peptides with short intervals, whereas the slow response was rather augmented by repeated application. Lowering the temperature markedly depressed the slow response, while the fast response remained almost unaffected. It is therefore likely that the fast and slow depolarizations are mediated by two different subtypes of tachykinin receptors or a single class of receptors linked with two different intracellular mechanisms. Measurement of tachykinins in several sympathetic ganglia by combined use of HPLC and radioimmunoassay revealed that the highest amount of SP occurs in the C-SMG where the content of SP (136.0 pmol/g protein) was higher than those of NKA (44.3) and NKB (18.7). SP thus appears to function as a major tachykinin in rat C-SMG.
Konishi
S
S
Department of Neuroscience, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Song
S Y
SY
Ogawa
T
T
Kanazawa
I
I
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology*; D013696:Temperature
D009467:Neuromuscular Depolarizing Agents; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B