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Pre-junctional factors influencing adrenergic transmission
Başlık:
Pre-junctional factors influencing adrenergic transmission
Yazar:
Docherty, James Roderick, author.
ISBN:
9780438057388
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (324 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: J. C. McGrath.
Özet:
The main object of this thesis was an investigation of pre-junctional factors influencing adrenergic transmission. In particular, the investigation concentrated on an examination of the respective roles of neuronal reuptake of noradrenaline (NA) and the pre-junctional alpha- adrenoceptor mediated feedback inhibition, and the interaction of these two factors. The preparation employed in most of these experiments was the pithed rat preparation, which allowed examination of several organ systems, cardiac sympathetic, cardiac vagus, vasopressor, somatic, vas deferens and anococcygeus. Preliminary experiments on the characteristics of the preparation led on to an examination of the cardiovascular and relaxant effects of several muscle relaxants, including analogues of pancuronium bromide, in a search for a muscle relaxant with relatively little side effects. In vitro experiments were carried out on the anococcygeus and vas deferens and the effects of sympathectomy or reserpinisation were examined on the responses of the vas deferens in preliminary experiments. Sympathetically innervated organs in the pithed rat were found to be very sensitive to low frequency stimulation, In particular, maximum cardioaccelerator responses were obtained at 0-5-1 Hz, so that in order to reduce the responses at these higher frequencies, the pithing rod electrode was sometimes moved to T2-T6, stimulating fewer fibres. The section examining the actions of uptake blockers included an examination of the effects of pancuronium, which was found to block neuronal uptake. Pancuronium had two effects in the pithed rat, a short lasting cardiovascular stimulation following injection, at least partly due to an indirect sympathomimetic action; and a longer lasting potentiation of responses to sympathetic stimulation. Pancuronium and cocaine had similar actions in potentiating sympathetic nerve-mediated responses of heart, blood vessels, vas deferens and anococcygeus. The response to a single stimulus pulse was most markedly potentiated, so that it was possible to use the cardioaccelerator response to a single stimulus as a sensitive index of uptake blocking potency in screening possible uptake blockers. Pancuronium and cocaine potentiated cardioaccelerator and pressor responses to NA, and reduced the cardioaccelerator but not the pressor responses to tyramine. Responses to isoprenaline or clonidine were unaffected. Following sympathectomy, responses to NA were not potentiated by pancuronium. Although the extraneuronal uptake blocker, corticosterone , failed to potentiate nerve-mediated responses of heart, blood vessels and vas deferens, it potentiated the pressor response to exogenous NA, suggesting a role for extraneuronal uptake in sparsely innervated tissues. The inhibitory effects of clonidine were compared with procedures which reduce the effector response to cardioaccelerator nerve stimulation in the pithed rat. The effect of clonidine was most marked against responses to stimulation with relatively short trains of pulses and or low frequencies of stimulation but a similar effect could be achieved by stimulating fewer fibres (T2-T6), by pre-treating the rats with reserpine or 6-OHDA or by acute administration of guanethidine or propranolol. Unlike the other procedures, however, clonidine could not abolish responses, The effects of clonidine were similar whether or not endogenous alpha-adrenoceptor mediated could be demonstrated. After blockade of neuronal NA uptake, the inhibitory effect of clonidine was undiminished when the effect of cocaine on the frequency/response curve was taken into account. It is concluded that with frequencies and train lengths within the physiological range, relative resistance to the inhibitory effect of clonidine is more dependent on post-junctional summation than on the development of pre-junctional facilitation or feedback mechanisms. Even with a single stimulus, however, the inhibitory effect of clonidine was limited, suggesting than a portion of transmitter release is inaccessible to such blockade. This applied to several other alpha-adrenoceptor agonists examined.
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684597.1) | 684597-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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