An electrophysiological study of the actions of angiotensin II at the sympathetic neuroeffector junction in the guinea-pig vas deferens.
1. The effects of angiotensin II on sympathetic neuroeffector transmission in the guinea-pig vas deferens have been investigated by the use of intracellular and focal extracellular recording techniques to measure indirectly, the release of adenosine 5'-triphosphate (ATP). 2. Angiotensin II (10-100 nM) did not alter the amplitude of the first excitatory junction potential (e.j.p.) in a train but increased the amplitude of subsequent e.j.ps. There was a corresponding increase in the probability of occurrence of extracellularly recorded evoked excitatory junction currents (e.j.cs). Spontaneous quantal transmitter release was unaffected by angiotensin II. 3. The enhancement of transmitter release produced by angiotensin II was prevented by the angiotensin receptor antagonist, saralasin. 4. The increase in transmitter release produced by angiotensin II was due to an increase in the probability of transmitter release from individual varicosities and not due to any detectable change in the configuration of the nerve terminal impulse or to the induction of repetitive firing. 5. There was no overall enhancement of e.j.ps or e.j.cs by angiotensin II in reserpinized tissues. Surprisingly, the predominant effect of angiotensin II in reserpinized vasa deferentia was to inhibit evoked transmitter release, an effect reversed by indomethacin (3 microM). 6. The results show that angiotensin II increases the release of sympathetic transmitter by activating prejunctional angiotensin II receptors. However, when the co-transmitter noradrenaline was depleted, angiotensin II now inhibited transmitter release indirectly, presumably by stimulating prostaglandin formation in the smooth muscle cells which then inhibited release transjunctionally.
Ziogas
J
J
University Department of Pharmacology, Oxford.
Cunnane
T C
TC
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004566:Electrodes; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation; D009451:Neuroeffector Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D012504:Saralasin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation
D011983:Receptors, Purinergic; D000804:Angiotensin II; D012110:Reserpine; D012504:Saralasin; D009638:Norepinephrine