NK₂ tachykinin receptors mediate contraction of the pig intravesical ureter: Tachykinin‐induced enhancement of non‐adrenergic non‐cholinergic excitatory neurotransmission

Abstract

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 NK2 receptor selective agonist [beta-Ala(8)]-NKA (4-10), all three induced contractions, with the following potency order: NKA > [beta-Ala(8) ]-NKA (4-10) > SP. [Sar(9), Met(O(2))(11)]-SP and senktide, selective agonists of the NK1 and NK3 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 x 10(-6) mol/L), atropine (10(-7) mol/L) and indomethacin (3 x 10(-6) mol/L), did not alter the contraction induced by a submaximal (10(-7) mol/L) dose of [beta-Ala(8)]-NKA (4-10). MEN 10,376 (10(-8)-10(-7) mol/L), a NK2 receptor antagonist, reduced the contraction to 3 x 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 NK1 and NK3 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 NK2 receptors located in the smooth muscle. SP and NKA exert an enhancement of the NANC excitatory neurotransmission of the pig intravesical ureter.

Neuronal and smooth muscle receptors involved in the PACAP‐ and VIP‐induced relaxations of the pig urinary bladder neck

“…Different peptides released from CSPA are involved in the nonadrenergic noncholinergic (NANC) neurotransmission of the urinary tract. Thus, in the pig intravesical ureter, neurokinin A (NKA) is involved in the NANC excitatory transmission (Bustamante et al, 2000), producing a smooth muscle contraction via activation of NK 2 receptors (Bustamante et al, 2001). VIP and PACAP produce relaxation in the urinary tract either by a direct action on the smooth muscle cells or by indirect effects mediated through NO release from autonomic intramural neurons.…”

Physiology and Pharmacology of the Human Ureter: Basis for Current and Future Treatments

“…It was demonstrated that tachykinins cause a direct contraction of the pig intravesical ureter via NK-2 receptors. SP and NKA were shown to enhance the NANC excitatory neurotransmission of the pig intravesical ureter [78] . Peptide-containing nerves VIP, NPY, CGRP and SP were all demonstrated particularly in the lower human ureter [11] .…”

Pre‐ and post‐junctional bradykinin B2 receptors regulate smooth muscle tension to the pig intravesical ureter

“…Nitric oxide (NO) and unknown nature mediator/s are involved in the non‐adrenergic non‐cholinergic (NANC) inhibitory neurotransmission of the pig intravesical ureter . Peptides as substance P or neurokinin A evoke a direct contraction through smooth muscle NK 2 receptors, whereas vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase‐activating polypeptide 38 (PACAP 38) relax the intravesical ureter through smooth muscle VIP/PACAP receptors …”

“…Nitric oxide (NO) and unknown nature mediator/s are involved in the non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission of the pig intravesical ureter. 18 Peptides as substance P or neurokinin A evoke a direct contraction through smooth muscle NK 2 receptors, 20 whereas vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase-activating polypeptide 38 (PACAP 38) relax the intravesical ureter through smooth muscle VIP/PACAP receptors. 21 In the current study, BK evoked a potent contraction on ureteral strip basal tension, which was not changed as a consequence of urothelium mechanical removal, thus suggesting the involvement of smooth muscle receptors in such a response.…”