The release of catecholamines by nerve stimulation from the guinea-pig vas deferens
Başlık:
The release of catecholamines by nerve stimulation from the guinea-pig vas deferens
Yazar:
Macrae, Iseabail Mhairi, author.
ISBN:
9780438053755
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (155 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: John Spence Gillespie.
Özet:
The nature of the motor transmitter in the guinea-pig vas deferens is still under debate. The transmitter was originally presumed to be noradrenaline (NA) since this tissue has a very dense adrenergic innervation. However, over the last 15 years several workers have rejected this proposal in favour of two transmitters only one of which is NA. The main aim of this project was to determine the site and possible function of DA found in this tissue. Experiments were designed to test whether DA, in addition to NA, was released in detectable quantities from the tissue during periods of transmural stimulation, and when this was confirmed, the site of origin of this amine was investigated i.e. noradrenergic nerves, dopaminergic nerves or chromaffin tissue. Later in the study when it was concluded from the results that DA was more likely to be solely a precursor for NA synthesis, further experiments were designed to study the effects of NA on the motor response. 1) In the early part of the project measures were taken to obtain the maximum possible recovery of CAs from the bathing medium. The detection system and extraction procedure were improved and the introduction of an antioxidant (Ascorbic Acid) plus a chelating agent (EDTA) to the Krebs medium dramatically increased the recovery of both CAs by preventing their chemical oxidation. 2) In the guinea-pig vas deferens, NA, but not DA was spontaneously released in detectable amounts. The overflow of NA was maximal immediately after setting-up the preparation but fell to a low level of around 1 ng per 6 min after 45 min. The high initial values were probably caused by damage to the nerves on the surface of the vas when the tissues were desheathed prior to being set-up in the organ bath. 3) The spontaneous overflow of NA was unaffected by uptake inhibitors DMI and 17,?-oestradiol combined with MAO inhibitor tranylcypromine but significantly increased in the presence of either potassium channel blocker TEA combined with DMI or PBA. A combination of these last three drugs, however, was ineffective in producing a significant increase in spontaneous NA overflow. A) Additional 'predicted' values for spontaneous overflow were calculated from CA recovery data in control conditions and in the presence of drugs. Values derived from control, TEA+DMI and PBA data were surprisingly close to the measured values while those for DMI+17beta-oestradipl+tranylcypromine and TEA+DMI+PBA were significantly higher. One possible explanation for the differences is that the low doses of CAs (10 ng) used in recovery samples gave rise to an increased spontaneous release of NA in the presence of these particular combinations of drugs. 5) Transmural stimulation (10 Hz, 2,700 stimuli) of pairs of guinea-pig vasa resulted in a substantial overflow of NA (30 ng). When tissues were stimulated on three occasions at 30 min intervals, a steady decline in the overflow of the second and third samples was detected. Insufficient DA was present in a single sample to allow its detection but this problem was overcome by combining 6 stimulation samples from two preparations. The amount of DA in the overflow was also expressed as a percentage of the total NA overflow i.e. the DA:NA ratio. 6) Since TTX almost completely abolished the overflow of both NA and DA it was concluded that both amines were derived from nerves. 7) DMI+17beta-oestradiol+tranylcypromine had no significant effect on NA overflow while TEA+DMI doubled and PBA produced a five-fold increase. Since DA overflow was increased to the same extent as NA by these drugs it was concluded that both amines were released from the same site i.e. noradrenergic nerves. From the low content of DA in overflows it is concluded that DA is present solely as a precursor for NA synthesis and not as a motor transmitter. 8) Repeated periods of transmural stimulation depleted the tissue of both NA and DA but the depletion of DA exceeded that of NA. The possible origin of this effect is discussed and the likeliest cause is believed to be the preferential release of DA which was demonstrated during nerve stimulation. The cause of this preferential release of DA is discussed. 9) The mechanical response and NA overflow were measured for short trains of 200 stimuli (20 sec) and for long trains of 2,700 stimuli (4 1/2 min) both at 10 Hz and the rate of NA overflow (pg/stim) was found to be significantly higher for short stimulation periods. The mechanical response with long stimulation trains lasted only some 20-30 sec yet the NA overflow after the first 20 sec of a long stimulation train continued at about 50% of the initial rate of overflow measured in the short stimulus train. 10) With repeated short stimulation periods (10 Hz, 200 stimuli) no decline in NA overflow was evident. This could not be correlated with either the first or second component of the biphasic mechanical response since both declined with successive stimulation periods. 11) Tissues Fuperfused with constant concentrations of NA did not maintain a contractile response and rapidly became desensitised to this amine. During this NA-induced desensitisation the nerve-stimulated motor response was undiminished and in fact potentiated. It was therefore concluded that NA was not the motor transmitter responsible for the twitch component of the mechanical response. The NA-induced potentiation of the mechanical response was mediated via a- adrenoceptors presumably located post-junctionally on the smooth muscle cells and was successfully reduced in the presence of phentolamine. Since potentiation was increased in the presence of a B-blocker it was concluded that NA also exerts an inhibitory effect via adrenoceptors which are either located post-junctionally or pre-junctionally on the nerve terminals containing the unknown motor transmitter.
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
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XX(684473.1) | 684473-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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