Differential distribution of functional alpha(1)-adrenergic receptor subtypes along the rat tail artery
2005
The rat tail artery has been used for the study of vasoconstriction mediated by α1A-adrenoceptors (ARs). However, rings from proximal segments of the tail artery (within the initial 4 cm, PRTA) were at least 3-fold more sensitive to methoxamine and phenylephrine ( n = 6–12; p < 0.05) than rings from distal parts (between the sixth and 10th cm, DRTA). Interestingly, the imidazolines N -[5-(4,5-dihydro-1 H -imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulfonamide hydrobromide (A-61603) and oxymetazoline, which activate selectively α1A-ARs, were equipotent in PRTA and DRTA ( n = 4–12), whereas buspirone, which activates selectively α1D-AR, was ≈70-fold more potent in PRTA than in DRTA ( n = 8; p < 0.05). The selective α1D-AR antagonist 8-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (BMY-7378) was ≈70-fold more potent against the contractions induced by phenylephrine in PRTA (p K B of ≈8.45; n = 6) than in DRTA (p K B of ≈6.58; n = 6), although the antagonism was complex in PRTA. 5-Methylurapidil, a selective α1A-antagonist, was equipotent in PRTA and DRTA (p K B of ≈8.4), but the Schild slope in DRTA was 0.73 ± 0.05 ( n = 5). The noncompetitive α1B-antagonist conotoxin ρ-TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not in PRTA. These results indicate a predominant role for α1A-ARs in the contractions of both PRTA and DRTA but with significant coparticipations of α1D-ARs in PRTA and α1B-ARs in DRTA. Semiquantitative reverse transcription-polymerase chain reaction revealed that mRNA encoding α1A- and α1B-ARs are similarly distributed in PRTA and DRTA, whereas mRNA for α1D-ARs is twice more abundant in PRTA. Therefore, α1-ARs subtypes are differentially distributed along the tail artery. It is important to consider the segment from which the tissue preparation is taken to avoid misinterpretations on receptor mechanisms and drug selectivities.
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