Abstract
The effects of the Ca2+ channel antagonists amlodipine, cobalt, diltiazem, nifedipine and verapamil and the local anaesthetic lignocaine were investigated on action potential conduction in and on evoked transmitter release from sympathetic nerves in the guinea-pig isolated vas deferens. Transmitter release was investigated by measurement of evoked (trains of pulses at 1 and 2 Hz, 0.1-0.5 ms supramaximal voltage) excitatory junction potentials (e.j.ps) using microelectrodes; tension was recorded simultaneously; tritium [3H] overflow from vasa preincubated (37 degrees C, 30 min) in Krebs solution containing either [3H]-noradrenaline (NA, 25 microCi ml-1, 2 X 10(-6) M NA) or [3H]-adenosine (50 microCi ml-1, 1 X 10(-6) M adenosine). Amlodipine (0.5-2 X 10(-4) M), verapamil (0.5-2 X 10(-4) M), diltiazem (1-8 X 10(-4) M), lignocaine (0.1-2 X 10(-3) M) and cobalt (2-6 X 10(-2) M) in descending order of potency, but not nifedipine (1-5 X 10(-3) M), increased the latency and inhibited, then abolished, the amplitude and number of action potentials in a concentration-dependent manner. Amlodipine (0.5-1 X 10(-4) M), verapamil (1-2 X 10(-4) M), diltiazem (1-5 X 10(-4) M) and cobalt (1 X 10(-3) M), in descending order of potency, but not nifedipine (5 X 10(-4) M), inhibited then abolished evoked e.j.ps in a concentration-dependent manner. Cobalt inhibited e.j.ps at a lower concentration than that (2-6 X 10(-2) M) required to block action potential conduction. In unstimulated tissues, the resting [3H] overflow following preincubation with [3H]-NA consisted largely of 4-hydroxy 3-methoxymandelic acid (VMA), 4-hydroxy 3-methoxy phenylglycol (MOPEG), 3,4 dihydroxyphenylglycol (DOPEG) and NA; stimulated tissues (300 pulses at 20 Hz, 0.5 ms supramaximal voltage) released mainly NA. Verapamil (0.1-1 X 10(-4) M), amlodipine (0.05-1 X 10(-4) M) and nifedipine (1-5 X 10(-4) M), but not cobalt (2 X 10(-3) M), increased, significantly, the resting overflow of 3H comprising mainly DOPEG. Cobalt (2 X 10(-3) M) inhibited, significantly, the stimulation-evoked overflow of 3H. Verapamil (1 X 10(-4) M) had little effect on the resting overflow of 3H following preincubation with [3H]-adenosine. Diltiazem (5 X 10(-4) M) and cobalt (2 X 10(-3) M) both inhibited evoked 3H overflow. Nifedipine (5 X 10(-4) M) was ineffective.(ABSTRACT TRUNCATED AT 400 WORDS)
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- Alberts P., Bartfai T., Stjärne L. Site(s) and ionic basis of alpha-autoinhibition and facilitation of "3H'noradrenaline secretion in guinea-pig vas deferens. J Physiol. 1981 Mar;312:297–334. doi: 10.1113/jphysiol.1981.sp013630. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BURNSTOCK G., HOLMAN M. E. The transmission of excitation from autonomic nerve to smooth muscle. J Physiol. 1961 Jan;155:115–133. doi: 10.1113/jphysiol.1961.sp006617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunnane T. C., Stjärne L. Frequency dependent intermittency and ionic basis of impulse conduction in postganglionic sympathetic fibres of guinea-pig vas deferens. Neuroscience. 1984 Jan;11(1):211–229. doi: 10.1016/0306-4522(84)90225-2. [DOI] [PubMed] [Google Scholar]
- Edwards C. The selectivity of ion channels in nerve and muscle. Neuroscience. 1982 Jun;7(6):1335–1366. doi: 10.1016/0306-4522(82)90249-4. [DOI] [PubMed] [Google Scholar]
- French A. M., Scott N. C. A comparison of the effects of nifedipine and verapamil on rat vas deferens. Br J Pharmacol. 1981 Jun;73(2):321–323. doi: 10.1111/j.1476-5381.1981.tb10424.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie J. S., Kirpekar S. M. The histological localization of noradrenaline in the cat spleen. J Physiol. 1966 Nov;187(1):69–79. doi: 10.1113/jphysiol.1966.sp008076. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graffe K. H., Stefano F. J., Langer S. Z. Preferential metabolism of (-) 3 H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol. 1973 May 15;22(10):1147–1160. doi: 10.1016/0006-2952(73)90231-1. [DOI] [PubMed] [Google Scholar]
- Göthert M., Nawroth P., Neumeyer H. Inhibitory effects of verapamil, prenylamine and D 600 on Ca2+-dependent noradrenaline release from the sympathetic nerves of isolated rabbit hearts. Naunyn Schmiedebergs Arch Pharmacol. 1979 Dec;310(1):11–19. doi: 10.1007/BF00499869. [DOI] [PubMed] [Google Scholar]
- Hay D. W., Wadsworth R. M. Local anaesthetic activity of organic calcium antagonists: relevance to their actions on smooth muscle. Eur J Pharmacol. 1982 Feb 5;77(4):221–228. doi: 10.1016/0014-2999(82)90122-4. [DOI] [PubMed] [Google Scholar]
- Sneddon P., Westfall D. P. Pharmacological evidence that adenosine triphosphate and noradrenaline are co-transmitters in the guinea-pig vas deferens. J Physiol. 1984 Feb;347:561–580. doi: 10.1113/jphysiol.1984.sp015083. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stjärne L., Astrand P. Discrete events measure single quanta of adenosine 5'-triphosphate secreted from sympathetic nerves of guinea-pig and mouse vas deferens. Neuroscience. 1984 Sep;13(1):21–28. doi: 10.1016/0306-4522(84)90256-2. [DOI] [PubMed] [Google Scholar]
- Takata Y., Kato H. Effects of Ca antagonists on the norepinephrine release and contractile responses of isolated canine saphenous veins to transmural nerve stimulation. Jpn J Pharmacol. 1984 Apr;34(4):397–409. doi: 10.1254/jjp.34.397. [DOI] [PubMed] [Google Scholar]
- Westfall D. P., Stitzel R. E., Rowe J. N. The postjunctional effects and neural release of purine compounds in the guinea-pig vas deferens. Eur J Pharmacol. 1978 Jul 1;50(1):27–38. doi: 10.1016/0014-2999(78)90250-9. [DOI] [PubMed] [Google Scholar]
- Wolchinsky C., Zsotér T. T. The effect of diltiazem on noradrenaline release. Br J Pharmacol. 1985 Jun;85(2):387–393. doi: 10.1111/j.1476-5381.1985.tb08873.x. [DOI] [PMC free article] [PubMed] [Google Scholar]