Potentiation of norepinephrine secretion by angiotensin II in the isolate rabbit iris-ciliary body.
The prejunctional effects of angiotensin II (AII) on stimulation-evoked secretion of 3H-norepinephrine (3H-NE) were investigated by in vitro methods in isolated, superfused rabbit iris-ciliary body preparations. AII (0.1-10 nM) concentration-dependently enhanced the field- stimulated release of 3H-NE (EC50 = 0.1 nM), nearly doubling evoked neurotransmitter release with no apparent effect on spontaneous 3H-NE efflux. The response to 1 nM AII was abolished by the selective AII receptor antagonist saralasin [( Sar1,Val5, Ala8]-angiotensin II; 500 nM), which alone did not modify 3H-NE overflow. AII-mediated effects on neurosecretion were partially additive to those of forskolin and were not potentiated by phosphodiesterase inhibition, suggesting that AII utilizes a mechanism other than increased cAMP synthesis to facilitate neurotransmitter release. AII also strongly enhanced calcium ionophore (A23187)-induced 3H-NE release in iris-ciliary body segments, indicating that AII can modulate calcium-dependent exocytosis at step(s) distal to calcium influx. These results demonstrate that sympathetic nerves in the rabbit eye contain prejunctional, facilitatory AII receptors, and support the possible involvement of the renin-angiotensin system in regulation of ocular sympathetic neurotransmission in vivo.
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Research Institute, University of Louisville School of Medicine 40292.
J E
JE
Jumblatt
R C
RC
Hackmiller
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D012504:Saralasin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000804:Angiotensin II; D005576:Colforsin; D000001:Calcimycin; D013779:Tetrodotoxin; D012504:Saralasin; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine