1993 (English)Doctoral thesis, comprehensive summary (Other academic)
The present study provides new insight into the pharmacology, the signal transduction mechanisms and the molecular biology of a2-adrenoceptors (a2-ARs) in black pigment cells (melanophores) of a teleost fish, the cuckoo wrasse (Labrus ossifagus L.). Stimulation of these receptors leads to an aggregation of intracellular pigment granules, which is the cellular mechanism underlying the ability of fishes to change color.
The pharmacology of the melanophore a2-AR is very similar to its mammalian counterparts. However, the melanophore a2-AR is unique in one respect, UK 14,304, a potent agonist at mammalian a2-ARs, is an antagonist in melanophores.
Noradrenaline and the selective a2-AR agonist B-HT 920 are pharmacologically heterogeneous regarding their ability to induce pigment aggregation. This may reflect that B-HT 920 and noradrenaline interact with different a2-AR sites.
Pigment aggregation induced by a2-ARs seems to involve multiplesignaling pathways. Attenuation of intracellular cAMP production and a subsequent reduction of protein kinase A activity may serve as one mechanism, and an additional signal mechanism may involve activation of a phosphatase.
An a2-adrenoceptor (a2p) from L. ossifagus skin mRNA was cloned. The deduced amino acid sequence showed significant homology with the human a2-ARs. When expressed in a mammalian cell line, the pharmacology of the <X2F was found to be very similar that of the in situ melanophore a2-ARs. The <X2F showed characteristics of both the human a2CIO and a2C4, indicating that <X2F may represent traces of an ancestral subtype.
Melanin-concentrating hormone (MCH) induces pigment aggregationthrough a unique receptor. However, MCH receptors and a2-ARs might share a common signal transduction mechanism, namely attenuation of cAMP production.
When melanophores are maintained in tissue culture media, the sensitivity to noradrenaline is increased and the sensitivity to MCH is decreased. This reciprocal change in sensitivity may be due to an increase in a2-AR coupling at the expense of MCH receptor couplingand/or to a down regulation of MCH receptors.
Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1993. , 66 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 396
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-27545Local ID: 12205ISBN: 91-7870-937-7OAI: oai:DiVA.org:liu-27545DiVA: diva2:248097
1993-09-17, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Cotecchia, Susanna, Professor
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.2009-10-082009-10-082012-07-23Bibliographically approved