Purine-induced depression of dorsal horn neurons in the cat spinal cord: enhancement by tachykinins.
The neurokinins, physalaemin, substance P, neurokinin A and bradykinin, were tested on the responses of single spinal neurons to the purines, adenosine 5'-triphosphate (ATP) and adenosine 5'-monophosphate and to GABA. Experiments were done on anaesthetized cats, recording extracellularly from functionally identified sensory neurons in the lumbar dorsal horn. All compounds were administered by iontophoresis. Neurokinins caused a slow, prolonged excitation which outlasted the period of application. Physalaemin was tested on responses to ATP in 24 units. In each case application of ATP caused either depression, excitation or a biphasic response when the application was not pre-conditioned by ejection of physalaemin. For 11 units, with ATP applications subthreshold to alter the on-going firing rate, such applications caused depression when they were preceded by administration of physalaemin. Three units were tested with ATP applications which caused the excitatory response; when the applications of ATP were preceded by ejection of physalaemin, there was then a depressant component in the response. In these 14 cases, the magnitude of the depression or of the depressant component of the response, was measured using currents which failed to produce depression in the absence of physalaemin ejection; the mean magnitude of this depression was 34.7 +/- 1.6% (+/- S.E.M.). With the 10 remaining units, responses to ATP were unaffected by application of physalaemin. The early components of the biphasic and excitatory responses were unaffected by physalaemin and hence it appeared to have a differential effect, enhancing only the depressant effects of ATP. The enhancement of depression was reversible, lasting up to 30 min following a single ejection. Neither control current nor glutamate mimicked the effect of physalaemin in the responses to application of ATP. The depressant response to adenosine 5'-monophosphate was also enhanced by physalaemin: ejections of adenosine 5'-monophosphate subthreshold to affect the on-going firing rate caused depression after physalaemin application in 3 of 8 units (average depression: 35.0 +/- 3.3%). On the other hand, depression induced by GABA was unaffected by physalaemin in every case (n = 8); in 4 of these cases GABA was tested on units for which purine-induced depression was enhanced by physalaemin. Thus, physalaemin preferentially affected depressant responses to ATP and to adenosine 5'-monophosphate.(ABSTRACT TRUNCATED AT 400 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002415:Cats; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000145:classification / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D010803:Physalaemin / Q000494:pharmacology; D011930:Reaction Time; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D009479:Neuropeptides; D015320:Tachykinins; D010803:Physalaemin; D013373:Substance P; D000249:Adenosine Monophosphate; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D001920:Bradykinin