Presynaptic alpha 2-autoinhibition in a vascular neuroeffector junction where ATP and noradrenaline act as co-transmitters.
1. alpha 2-Autoinhibition of transmitter release was investigated in the largest rami caecales of the rabbit ileocolic artery. Vasoconstriction, elicited by electrical field stimulation or by exogenous agonists, was measured as an increase in perfusion pressure. 2. Short periods of electrical stimulation elicited monophasic vasoconstriction, whereas longer periods (greater than 10 s) produced biphasic vasoconstriction. Prazosin had no significant effect on the first component of the biphasic vasoconstriction elicited by electrical stimulation, but did reduce the second component at higher frequencies. alpha, beta-Methylene ATP significantly attenuated the first component whilst the second component was relatively resistant. 3. The alpha 2-adrenoceptor antagonist yohimbine did not change responses evoked by very short pulse trains (less than 2 s) but enhanced responses to longer pulse trains. When vasoconstriction was biphasic, both phases were potentiated by yohimbine. 4. The results indicate that the vasoconstriction elicited by brief trains of sympathetic nerve impulses is mainly or exclusively mediated by ATP, whereas at longer pulse trains a noradrenergic component comes into play. The potentiation produced by yohimbine is due to interruption of presynaptic alpha 2-adrenoceptor-mediated autoinhibition of transmitter release. The autoinhibition affects both purinergic and adrenergic components of sympathetic neurotransmission.
Bulloch
J M
JM
Pharmakologisches Institut, Universität Freiburg, Federal Republic of Germany.
Starke
K
K
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation; D009451:Neuroeffector Junction / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D018377:Neurotransmitter Agents; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine; D011224:Prazosin