الفهرس | Only 14 pages are availabe for public view |
Abstract This study was conducted to fulfill two objectives. The first objective was to investigate the effects of dopamine and D1-like agonists on neuromuscular transmission, as well as demonstrating the influence of other co-transmitters and/or neuromodulators such as adenosine triphosphate (ATP), adenosine and nicotine at the neuromyal junction. The second objective was to explore potential interactions and collaborations that may develop among dopamine and the aforementioned co-transmitters and/ or neuromodulators. In order to satisfy these goals in vitro experiments were conducted using the isolated rat phrenic hemi-diaphragm preparation which was stimulated either directly or indirectly through the stimulation of the phrenic nerve. The parameter used to assess neuromuscular transmission at low frequency was the percentage change in the amplitude of nerve-evoked or direct muscle twitches, while at high frequency (tetanic stimulation) the parameters evaluated were percentage change in amplitude of first phase of tetanic contraction, negative tetanic fade and post-tetanic potentiation. The principal findings of the current study can be summarized as follows; I. Effect of Individual Neuromodulators on the Contraction of Isolated Rat Phrenic Hemi-Diaphragm Preparation 1. Dopamine and D1-Like Agonist; SKF 81297 i- Indirect Muscle Twitches Dopamine induced a significant augmentation of the amplitude of nerve-elicited muscle twitches at all doses and with all the different experimental protocols adopted (Designs A, B and C). The dopamine-mediated potentiation was maintained in presence of the β-adrenergic antagonist; propranolol, but was eliminated in presence of the selective D1-like receptor antagonist; SCH23390. Thus it could be concluded that dopamine produces a facilitatory effect on neuromuscular transmission possibly via D1-like receptors rather than β-adrenergic receptors. The selective D1-like agonist; SKF 81297, also demonstrated a statistically evident enhancement of the indirect muscle twitches, exhibiting higher percentages of potentiation at a lower dose range; 1 – 32 μM, as compared to dopamine; 1 - 256 μM, possibly due to its higher selectivity. ii- Direct Muscle Twitches The amplitude of direct muscle twitches was significantly increased by dopamine and the augmentation was sustained in presence of propranolol but was totally abolished by SCH 23390. Therefore it can be concluded that the dopamine-mediated facilitation of direct stimulation is mediated solely by the D1-like receptors localized within the diaphragm muscle. |