Effects of tyramine on noradrenaline outflow and electrical responses induced by field stimulation in the perfused rabbit ear artery.
In the perfused rabbit ear artery the basal outflows of noradrenaline (NA) and 3,4-dihydroxyphenylglycol (DOPEG) were less than 1 ng g-1 and 1-2 ng g-1 wet weight of tissue respectively. Field stimulation increased outflows of NA and DOPEG in a frequency-dependent manner, and they reached the maximum value at frequencies over 5 Hz. Tyramine (1 X 10(-6) -1 X 10(-4) M) increased basal outflow of NA and DOPEG, in a dose-dependent manner. This effect was not blocked by tetrodotoxin (TTX, 3 X 10(-7) M), but was prevented by pretreatment with 6-hydroxydopamine (6-OHDA). Tyramine increased the field stimulation-induced outflow of NA but not that of DOPEG in a dose-dependent manner. Cocaine (1 X 10(-5) M) reduced the increased outflow of NA induced by tyramine at rest and during field stimulation, without modifying DOPEG-outflow. Guanethidine (5 X 10(-6) M), increased outflows of NA and DOPEG at rest, and reduced the NA outflow induced by field stimulation. Pretreatment with guanethidine (5 X 10(-6) M) did not block the action of tyramine on NA and DOPEG basal outflows. Additional application of guanethidine during the presence of tyramine did reduce the outflow of NA induced by field stimulation, but did not modify the outflow of NA and DOPEG at rest. Tyramine at concentrations over 1 X 10(-5) M depolarized the smooth muscle membrane of the rabbit ear artery. After chemical denervation with 6-hydroxydopamine (6-OHDA) the depolarizing action of tyramine was reduced. Tyramine-induced depolarization was attenuated by prazosin (5 X 10(-6) M) or phentolamine (5 X 10(-6) M), but not by guanethidine (5 X 10(-6) M). In 6-OHDA-denervated tissues, tyramine-induced depolarization was attenuated by phentolamine but not by prazosin. Field stimulation evoked excitatory junction potential (e.j.p.), slow depolarization and spike potential in the rabbit ear artery. Tyramine reduced, while guanethidine blocked these electrical responses. Tyramine did not alter the facilitation process of e.j.ps. In tissues pretreated with guanethidine, tyramine evoked either no electrical response or a slow depolarization during field stimulation. The slow depolarization was blocked by prazosin. Tyramine reduced the NA content of tissues in a dose-dependent manner (by 31% at 10(-4) M). Guanethidine (5 X 10(-6) M) reduced the NA content by 20%. 10 We conclude that in the rabbit ear artery, tyramine depolarizes the smooth muscle membrane indirectly by releasing neuronal NA which acts on alpha-adrenoceptors, and directly by an action on the smooth muscle cells. Two NA compartments (guanethidine-sensitive and tyramine-sensitive NA) could be identified. Field stimulation releases the former with associated generation of ej.p. and slow depolarization whilst the release of the latter is not accompanied by ej.p. generation.
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology*
D013779:Tetrodotoxin; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D014439:Tyramine; D006145:Guanethidine