Human tachykinin NK2 receptor: a comparative study of the colon and urinary bladder.
1. The present study compared the binding and functional characteristics of tachykinin NK2 receptors in human detrusor muscle with those in human colon circular muscle. 2. In radioligand binding studies, similar KD values were observed for tachykinin NK2 receptor radioligands [125I]-neurokinin (NK) A, [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10,]NKA(4-10) and [3H]-SR48968 in both human colon circular muscle (0.28-1.1 nmol/L) and human bladder detrusor (0.49-0.91 nmol/L), suggesting binding was primarily to tachykinin NK2 receptors. Receptor capacity (Bmax) was greater in colon compared with detrusor muscle. 3. In functional studies of isolated smooth muscle contraction, there was an excellent positive correlation between human bladder detrusor and colon circular muscle with respect to in vitro contractile potency (r = 0.97) and maximum responses (r = 0.98) to tachykinins, selective tachykinin receptor ligands and l-Ala-substituted NKA(4-10) analogues. 4. Species differences between the human and rat tachykinin NK2 receptors were apparent as observed by a low correlation for potency (r = 0.77) and efficacy (r = 0.32) of l-Ala-substituted analogues in isolated smooth muscle contractile studies. 5. Minor differences observed in the affinity and potency of NK2 receptor agonists between colon and bladder are dependent on the tissue of interest, the receptor-effector coupling and the presence of other tachykinin receptors. Overall, the NK2 receptors of human colon and urinary bladder smooth muscle appear pharmacologically identical.
Warner
Fiona J
FJ
School of Physiology and Pharmacology, University of New South Wales, Sydney, New South Wales, Australia. bmbfjw@bmb.leeds.ac.uk
Miller
Robert C
RC
Burcher
Elizabeth
E
D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015288:Neurokinin A / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D001549:Benzamides; D010446:Peptide Fragments; D010880:Piperidines; D018041:Receptors, Neurokinin-2; C073839:SR 48968; D015288:Neurokinin A; C056408:neurokinin A(4-10)