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Marihuana-derived material: biochemical studies of the ocular responses
Abstract:
Some biochemical factors of the iris-ciliary body of the rabbit have been examined for effects induced by water-soluble marihuana-derived material (MDM). Adenylate cyclase activity and sensitivity to beta-adrenergic agonists were unchanged, as measured 4 hours after MDM administration in vivo. Magnesium-dependent and anion-sensitive, but not sodium-potassium, ATPase activities were inhibited 6 hours after MDM administration in vivo, although they were unaffected by in vitro incubation. Topical administration of a potent substance P antagonist had no effect on the time course or magnitude of intravenous MDM-induced ocular effects in rabbit. Intravenously administered sugars antagonized the effects of MDM on intraocular pressure. A variety of drugs which display a range of biochemical effects varying from beta-adrenergic receptor agonism, to alteration of glycoprotein residues were employed. None of the agents employed, ranging from cAMP modifiers to protein synthesis blockers, had any effect on the MDM-induced response. It is apparent that the mechanism underlying the ocular hypotensive effect of MDM does not reside in mediation through adenylate cyclase, ATPase or substance P, but rather through a mechanism mediated by terminal sugar moieties on the molecule. The data suggest that modification of the surface membrane glycoprotein residues on the ciliary epithelium can induce marked alterations in aqueous humor flow rate.
Insights
Marihuana-derived material (MDM) lowers intraocular pressure by affecting sugar moieties on ciliary epithelium glycoproteins, not through common biochemical pathways. This suggests a novel mechanism for ocular hypotensive effects.
Area of Science:
- Ocular pharmacology
- Biochemistry
- Ophthalmology
Background:
- Water-soluble marihuana-derived material (MDM) is known to affect ocular physiology.
- The precise biochemical mechanisms underlying MDM's ocular effects, particularly its hypotensive properties, remain largely uncharacterized.
Purpose of the Study:
- To investigate the biochemical factors in the rabbit iris-ciliary body affected by marihuana-derived material (MDM).
- To elucidate the mechanism of MDM-induced ocular hypotensive effects.
Main Methods:
- In vivo administration of MDM to rabbits.
- Measurement of adenylate cyclase and ATPase activities in ocular tissues.
- Assessment of responses to beta-adrenergic agonists and substance P antagonists.
- Evaluation of the effects of sugars and various pharmacological agents on MDM-induced ocular changes.
Main Results:
- MDM administration did not alter adenylate cyclase activity or beta-adrenergic agonist sensitivity.
- Magnesium-dependent and anion-sensitive ATPase activities were inhibited 6 hours post-MDM administration.
- Substance P antagonists and various drugs, including cAMP modifiers and protein synthesis blockers, did not affect MDM-induced ocular responses.
- Intravenously administered sugars antagonized MDM's effect on intraocular pressure.
Conclusions:
- The ocular hypotensive effect of MDM is not mediated by adenylate cyclase, ATPase, or substance P.
- The mechanism appears to involve terminal sugar moieties on the MDM molecule.
- Alterations in ciliary epithelium surface membrane glycoprotein residues may significantly influence aqueous humor flow rate.