title: Naphazoline-induced neuroendocrine changes: increases in ANP and cGMP levels, but suppression of NE, 3H-NE, and cAMP levels in rabbit eyes.
abstract: The objective of this study was to determine whether naphazoline, an alpha 2 (alpha2)/imidazoline (I1) agonist, can alter endogenous levels of atrial natriuretic peptide (ANP) and norepinephrine (NE) in aqueous humor and cyclic nucleotide (cAMP, cGMP) accumulation and NE overflow in the iris-ciliary body (ICB) of the rabbit eye. Topical naphazoline (25, 75, and 250 microg) caused a dose-dependent elevation of the ANP levels (36, 54, and 137 pg/ml, respectively) in aqueous humor. This effect was antagonized by pretreatment with efaroxan, an antagonist of I1/alpha2 receptors. Another alpha2/I1 agonist, moxonidine (75 microg topically), caused significant increases in ANP levels in aqueous humor, whereas other relatively selective alpha2-adrenergic receptor agonists, brimonidine (50 microg topically) and oxymetazoline (75 microg topically), did not. In naphazoline (75 microg) pretreated eyes, the NE levels in aqueous humor were attenuated by 36% (from 6.0 to 3.8 pg/ml). Furthermore, naphazoline (1, 10, and 100 micromol/l) caused a dose-related inhibition of NE release from ICBs: 25, 45, and 80%, respectively. The isoproterenol (1 micromol/l) stimulated cAMP accumulation was inhibited 53% by naphazoline (100 micromol/l). In contrast, naphazoline significantly increased the cGMP levels in ICBs. These data demonstrate that naphazoline acts on I1 receptors to increase ANP and to reduce NE levels in aqueous humor. The former effect could also contribute to elevation of cGMP levels and inhibition of cAMP accumulation in the ICB. Further studies will be required to determine if elevation of ANP levels is a critical component of naphazoline-induced alteration of aqueous humor dynamics.
authors.affiliation: Department of Pharmacology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, USA.
authors.forename: Miller J
authors.initials: MJ
authors.lastname: Ogidigben
authors.forename: Teh-Ching
authors.initials: TC
authors.lastname: Chu
authors.forename: David E
authors.initials: DE
authors.lastname: Potter
mesh_terms: D000287:Administration, Topical; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005123:Eye / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009278:Naphazoline / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D014316:Tritium
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D014316:Tritium; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D009278:Naphazoline; D006152:Cyclic GMP; D009638:Norepinephrine