Prejunctional receptors and second messengers for angiotensin II in the rabbit iris-ciliary body.
Angiotensin II has been shown to act prejunctionally to facilitate sympathetic neutrotransmission in various tissues including the iris-ciliary body. In the present study, we characterized the prejunctional angiotensin II receptor subtype and its signal transduction pathway in the rabbit iris-ciliary body. Angiotensin II caused concentration-dependent facilitation of electrically evoked [3H]-norepinephrine overflow from the isolated, superfused rabbit iris-ciliary body without affecting basal tritium efflux. Responses to angiotensin II were antagonized by saralasin and DuP753 but not by PD123177 indicating that prejunctional angiotensin II receptors of the AT1-subtype mediate the facilitation of evoked [3H]-norepinephrine release. The non-selective cyclic nucleotide phosphodiesterase inhibitor, isobutylmethyl xanthine enhanced the angiotensin II response whereas the cAMP-specific phosphodiesterase inhibitor, RO-20-1724 had no effect. In the presence of 8-bromo-cGMP, responses elicited by angiotensin II were significantly (P < 0.01) greater than that caused in the absence of 8-bromo-cGMP. In contrast, 8-bromo-cAMP had no effect on the angiotensin II-induced response. Guanylate cyclase inhibitors, methylene blue and LY83583 abolished angiotensin II-induced enhancement of [3H]-norepinephrine overflow without affecting basal tritium efflux. Taken together, these results suggest that cGMP could be involved in the angiotensin II response. Neither phospholipase C inhibitors (neomycin, 2-nitro-4-carboxyphenyl-N,N-diphenyl carbamate and phenylmethylsulfonyl fluoride) nor an inhibitor of protein kinase C (staurosporine) had any significant effect on the angiotensin II response, indicating that metabolites of inositol phospholipid metabolism or activation of protein kinase C are not involved in the response to this peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohia
S E
SE
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Research Institute 40292.
Jumblatt
J E
JE
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002924:Ciliary Body / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D007498:Iris / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010716:Phosphatidylinositols / Q000502:physiology; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology; D015290:Second Messenger Systems; D015398:Signal Transduction; D013268:Stimulation, Chemical
D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000242:Cyclic AMP; D012504:Saralasin; D006152:Cyclic GMP; D009638:Norepinephrine