Differential distribution of functional alph}1-adrenergic receptor subtypes along the rat tail artery.
The rat tail artery has been used for the study of vasoconstriction mediated by alpha(1A)-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-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulfonamide hydrobromide (A-61603) and oxymetazoline, which activate selectively alpha(1A)-ARs, were equipotent in PRTA and DRTA (n = 4-12), whereas buspirone, which activates selectively alpha(1D)-AR, was approximately 70-fold more potent in PRTA than in DRTA (n = 8; p < 0.05). The selective alpha(1D)-AR antagonist 8-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (BMY-7378) was approximately 70-fold more potent against the contractions induced by phenylephrine in PRTA (pK(B) of approximately 8.45; n = 6) than in DRTA (pK(B) of approximately 6.58; n = 6), although the antagonism was complex in PRTA. 5-Methylurapidil, a selective alpha(1A)-antagonist, was equipotent in PRTA and DRTA (pK(B) of approximately 8.4), but the Schild slope in DRTA was 0.73 +/- 0.05 (n = 5). The noncompetitive alpha(1B)-antagonist conotoxin rho-TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not in PRTA. These results indicate a predominant role for alpha(1A)-ARs in the contractions of both PRTA and DRTA but with significant coparticipations of alpha(1D)-ARs in PRTA and alpha(1B)-ARs in DRTA. Semiquantitative reverse transcription-polymerase chain reaction revealed that mRNA encoding alpha(1A)- and alpha(1B)-ARs are similarly distributed in PRTA and DRTA, whereas mRNA for alpha(1D)-ARs is twice more abundant in PRTA. Therefore, alpha(1)-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.
Kamikihara
Susana Y
SY
Department of Pharmacology, Instituto de Biociências, UNESP, Botucatu, São Paulo, Brazil, 18618-000.
Mueller
André
A
Lima
Vanessa
V
Silva
Aderbal R T
AR
da Costa
Isabela Bazzo
IB
Buratini
José
J
Pupo
André S
AS
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology; D020916:Conotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013623:Tail / Q000098:blood supply
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D020916:Conotoxins; D010879:Piperazines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D017366:Serotonin Receptor Agonists; C477745:conotoxin rho-TIA; D010656:Phenylephrine; D012313:RNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C053428:BMY 7378; D002065:Buspirone