Premium
NK 2 tachykinin receptors mediate contraction of the pig intravesical ureter: Tachykinin‐induced enhancement of non‐adrenergic non‐cholinergic excitatory neurotransmission
Author(s) -
Bustamante Salvador,
Orensanz Luis M.,
Barahona María Victoria,
GarcíaSacristán Albino,
Hernández Medardo
Publication year - 2001
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.1007
Subject(s) - tachykinin receptor , endocrinology , medicine , neurokinin a , substance p , phentolamine , agonist , receptor , neurotransmission , ppads , receptor antagonist , contraction (grammar) , muscarinic acetylcholine receptor , antagonist , chemistry , neuropeptide
The current study was designed to characterize the functionally active tachykinin receptors involved in tachykinin‐elicited contractions in the pig intravesical ureter, and to investigate the possible modulation exerted by the natural tachykinins substance P (SP) and neurokinin A (NKA) on the non‐adrenergic non‐cholinergic (NANC) excitatory ureteral neurotransmission. In pig intravesical ureteral strips pretreated with phosphoramidon (10 −5 mol/L) to block the endopeptidase activities, isometric force recordings showed that SP, NKA, and the NK 2 receptor selective agonist [β‐Ala 8 ]‐NKA (4–10), all three induced contractions, with the following potency order: NKA > [β‐Ala 8 ]‐NKA (4–10) > SP. [Sar 9 , Met(O 2 ) 11 ]‐SP and senktide, selective agonists of the NK 1 and NK 3 receptors, respectively, failed to modify the ureteral tone. Urothelium removal and incubation with tetrodotoxin (10 −6 mol/L), phentolamine (10 −7 mol/L), propranolol (3 × 10 −6 mol/L), atropine (10 −7 mol/L) and indomethacin (3 × 10 −6 mol/L), did not alter the contraction induced by a submaximal (10 −7 mol/L) dose of [β‐Ala 8 ]‐NKA (4–10). MEN 10,376 (10 −8 –10 −7 mol/L), a NK 2 receptor antagonist, reduced the contraction to 3 × 10 −8 mol/L NKA. GR 82334 (10 −6 –10 −5 mol/L) and SR 142801 (10 −8 –10 −7 mol/L), selective antagonists of the NK 1 and NK 3 receptors, respectively, did not modify that contraction. In pig intravesical ureteral strips in NANC conditions, SP and NKA induced a potentiation of the contractions to electrical field stimulation (EFS) and to exogenous ATP. The results suggest that the tachykinins evoke a direct contraction of pig intravesical ureteral strips through NK 2 receptors located in the smooth muscle. SP and NKA exert an enhancement of the NANC excitatory neurotransmission of the pig intravesical ureter. Neurourol. Urodynam. 20:297–308, 2001. © 2001 Wiley‐Liss, Inc.