Characterization of α1-Adrenoceptor Subtypes in the Eye

Wikberg-Matsson, Anna; Uhlén, Staffan; Wikberg, Jarl E. S.

doi:10.1006/exer.1999.0753

Cited by 56 publications

(34 citation statements)

References 30 publications

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“…Only minimal ␣ 1D -adrenoceptor gene transcription is seen. In accordance with these findings, binding studies also demonstrate a predominance of the ␣ 1A -adrenoceptor over the ␣ 1B -adrenoceptor subtype in the iris of rabbits, with no ␣ 1D -adrenoceptors found (Nakamura et al, 1999;Wikberg-Matsson et al, 2000). However, functional studies concerning the role of these adrenoceptor subtypes are incomplete.…”

Section: Discussionmentioning

confidence: 63%

α1A-Adrenoceptors Mediate Sympathetically Evoked Pupillary Dilation in Rats

Koss²

2002

The Journal of Pharmacology and Experimental Therapeutics

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Evidence suggests that in some species (cats, rabbits, and possibly humans) ␣-adrenoceptors in the iris dilator muscle are "atypical" in that they cannot be readily classified by conventional criteria. This study was undertaken in an attempt to characterize the ␣-adrenoceptor subtype(s) mediating sympathetically elicited mydriasis in rats. Frequency-response pupillary dilator curves were generated by stimulation of the preganglionic cervical sympathetic nerve (1-32 Hz) in pentobarbital-anesthetized rats. Evoked responses were inhibited by systemic administration of nonselective ␣-adrenergic antagonists, phentolamine (0.3-10 mg/ kg) and phenoxybenzamine (0.03-1 mg/kg). The selective ␣ 1 -adrenergic antagonist, prazosin (0.01-1 mg/kg), also was effective, although ␣ 2 -adrenergic antagonism with rauwolscine (0.1-1 mg/kg) was not. ␣ 1A -Adrenoceptor-selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1-1 mg/kg) and 5-methylurapidil (0.1-1 mg/kg), as well as the ␣ 1D -adrenoceptor-selective antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1-3 mg/kg), were used to determine the subtype(s) involved. Evoked mydriasis was significantly antagonized by both WB-4101 and 5-methylurapidil but not by BMY-7378. These results suggest that, unlike some other species, adrenoceptors in the rat iris dilator mediating neurogenic mydriasis are "typical" and, in addition, can be characterized as being primarily of the ␣ 1A -adrenoceptor subtype.

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Section: Discussionmentioning

confidence: 63%

α1A-Adrenoceptors Mediate Sympathetically Evoked Pupillary Dilation in Rats

Koss²

2002

The Journal of Pharmacology and Experimental Therapeutics

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“…The anterior segment of the porcine eye has an acceptable degree of anatomical and ultrastructural resemblance with the human eye (Bachmann et al 2006), and isolated porcine eyes (WikbergMatsson et al 2000;Wikberg-Matsson & Simonsen 2001) or isolated porcine iris muscles (Toda et al 1999) are established models for investigating ocular adrenoceptors (Toda et al 1999;Wikberg-Matsson et al 2000;Wikberg-Matsson & Simonsen 2001). In addition, for an intracameral mydriatic to be usable in humans safety issues, possible adverse reactions et cetera also have to be addressed.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of adrenergic β‐receptors enhances mydriasis in a porcine eye model

Janbaz

Lundberg

Behndig

2011

Acta Ophthalmologica

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Abstract.Purpose: To compare the mydriatic effect of intracamerally injected isoprenaline plus phenylephrine to phenylephrine alone and to epinephrine in a porcine eye model, aiming to eventually find the best combination of adrenergic substances for surgical mydriasis in humans.Methods: In this study, we used 89 intact eyes from newly slaughtered pigs, pretreated with 2.0 mg of intracameral acetylcholine. After waiting 60 seconds for miosis to develop, 0.15 ml 0.3% isoprenaline and 0.15 ml 3.0% phenylephrine were injected sequentially with a 90‐second interval in 21 eyes. In another 22 eyes, the same substances were given in the reverse order. In 20 eyes, 0.15 ml of 0.025% epinephrine was injected, and as a negative control 0.15 ml of balanced salt solution was injected in 26 eyes. The pupils were filmed during the treatments, and the mean pupil diameters were measured every 15 seconds from the video recordings.Results: Phenylephrine injected after isoprenaline had a larger mydriatic effect than epinephrine (p < 0.01). Without isoprenaline pretreatment, the mydriatic effect of phenylephrine was significantly smaller than that of epinephrine (p < 0.05). Isoprenaline also exhibited a small mydriatic effect of its own.Conclusions: The β‐receptor stimulator isoprenaline enhances the mydriatic effect of intracameral phenylephrine, indicating a role for the β‐receptor in the mydriatic response. Mydriasis mediated by β‐receptors may explain why nonspecific adrenergic stimulators such as epinine and epinephrine can have larger mydriatic effects than the specific α1‐receptor stimulator phenylephrine.

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“…13,14 For instance, iris dilator muscle contracts in response to stimulation of α 1A -, α 1B -or α 1L -adrenoceptors. [22][23][24] Vascular smooth muscles express all of α 1A -, α 1B -and α 1D -adrenoceptors.…”

Section: 10mentioning

confidence: 99%

“…11 The genes encoding the first three subtypes have been identified whereas the α 1L -subtype was recently identified as one phenotype derived from the α 1A -adrenoceptor gene. 12 There coexist multiple α 1 -adrenoceptor subtypes in eyes, 13,14 and phenylephrine nonselectively stimulates these receptors.…”

Section: Introductionmentioning

confidence: 99%