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 (α₂)/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 inthe iris-ciliary body (ICB) of the rabbit eye. Topical naphazoline (25, 75, and 250 µg) 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/α₂ receptors. Another α₂/I₁ agonist, moxonidine (75 µg topically), caused significant increases in ANP levels in aqueous humor, whereas other relatively selective α₂-adrenergic receptor agonists, brimonidine (50 µg topically) and oxymetazoline (75 µg topically), did not. In naphazoline (75 µg) 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 µmol/l) caused a dose-related inhibition of NE release from ICBs: 25, 45, and 80%, respectively. The isoproterenol (1 µmol/l) stimulated cAMP accumulation was inhibited 53% by naphazoline (100 µmol/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.

Participation of Prostaglandin E2 Receptor in Nasal Congestion of Brown Norway Rats

“…A potent vasoconstrictor, naphazoline, showed inhibition of cAMP accumulation 15) and suppressed nasal congestion induced by TXA 2 analog and leukotriene D 4 (LTD 4 ). 16) On the other hand, vasodilation is mediated by EP 4 receptor coupled to an increase of cAMP.…”

Ocular Hypotensive Action of Topical Flunarizine in the Rabbit: Role of ς1Recognition Sites

“…The inhibition of cAMP production by several mediators may require, in the autonomic nervous system, the previous activation of ␤-adrenergic receptors, whereas these compounds, per se, do not influence significantly adenylyl cyclase activity (Endoh, 1995). In the irisciliary body preparation, flunarizine and (ϩ)-pentazocine behave as the opioid agonists (Moore and Potter, 2001) or naphazoline (Ogidigben et al, 2002) and moxonidine (Ogidigben et al, 1994), which have no effect on basal cAMP production.…”

Rationale for naphazoline effects in-depth study

“…In addition, an experiment in rabbit eye showed a reduced aqueous humor flow rate in the eye chamber [30]. Further experimental studies have shown that naphazoline topical application in rabbit eye leads to an increase of endogenous atrial natriuretic peptide and decrease of noradrenaline in the cornea, and significantly increased cyclic nucleotides (cAMP, cGMP) through interaction with imidazoline receptors [29].…”