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Evidence for different pharmacological targets for imidazoline compounds inhibiting settlement of the barnacle Balanus improvisus
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy. (Pharmacognosy)
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2005 (English)In: Journal of Experimental Zoology, ISSN 0022-104X, E-ISSN 1097-010X, Vol. 303A, no 7, 551-562 p.Article in journal (Refereed) Published
Abstract [en]

We describe the effect of eight different imidazoline/guanidinium compounds on the settlement and metamorphosis of larvae of the barnacle Balanus improvisus. These agents were chosen on the basis of their similar pharmacological classification in vertebrates and their chemical similarity to medetomidine and clonidine, previously described as highly potent settlement inhibitors (nanomolar range). Seven of the tested compounds were found to inhibit settlement in a dose-dependent manner in concentrations ranging from 100 nM to 10 microM without any significant lethal effects. In vertebrate systems these substances have overlapping functions and interact with both alpha-adrenoceptors as well as imidazoline binding sites. Antagonizing experiments using the highly specific alpha(2)-antagonist methoxy-idazoxan or agmatine (the putative endogenous ligand at imidazoline receptors) were performed to discriminate between putative pharmacological mechanisms involved in the inhibition of cyprid settlement. Agmatine was not able to reverse the effect of any of the tested compounds. However, methoxy-idazoxan almost completely abolished the settlement inhibition mediated by guanabenz (alpha(2)-agonist, I(2) ligand), moxonidine (alpha(2)-agonist, I(1) ligand) and tetrahydrozoline (alpha-agonist, I(2) ligand). The actions of cirazoline (alpha(1)-agonist, I(2) ligand) BU 224 (I(2) ligand) and metrazoline (I(2) ligand) were not reversed by treatment with methoxy-idazoxan. These results suggest that the settlement inhibition evoked by the I(2) ligands and alpha(2)-agonists used in this study of the neurologically simple but well-organized barnacle larva is mediated through different physiological targets important in the overall settlement process.

Place, publisher, year, edition, pages
2005. Vol. 303A, no 7, 551-562 p.
Keyword [en]
Adrenergic Agonists/*pharmacology, Adrenergic alpha-Antagonists/pharmacology, Agmatine/pharmacology, Analysis of Variance, Animals, Comparative Study, Dose-Response Relationship; Drug, Idazoxan/pharmacology, Imidazoles/pharmacology, Imidazolines/antagonists & inhibitors/chemistry/*pharmacology, Metamorphosis; Biological/*drug effects/physiology, Movement/*drug effects/physiology, Research Support; Non-U.S. Gov't, Thoracica/*drug effects/*physiology
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-102052DOI: 10.1002/jez.a.163PubMedID: 15945078OAI: oai:DiVA.org:uu-102052DiVA: diva2:213887
Available from: 2009-04-29 Created: 2009-04-29 Last updated: 2010-05-26Bibliographically approved

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