DIFFERENT CA2-INDUCED CONTRACTION IN CIRCULAR MUSCLE OF GUINEA-PIG COLON( INFLUX PATHWAYS MEDIATE TACHYKININ RECEPTOR)

Citation
V. Zagorodnyuk et al., DIFFERENT CA2-INDUCED CONTRACTION IN CIRCULAR MUSCLE OF GUINEA-PIG COLON( INFLUX PATHWAYS MEDIATE TACHYKININ RECEPTOR), European journal of pharmacology, 255(1-3), 1994, pp. 9-15
Citations number
28
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
255
Issue
1-3
Year of publication
1994
Pages
9 - 15
Database
ISI
SICI code
0014-2999(1994)255:1-3<9:DCCICM>2.0.ZU;2-N
Abstract
We used an electrophysiological approach (single sucrose gap) to compa re the mechanism of action of selective tachykinin NK1 and NK2 recepto r agonists ([Sar(9)]substance P sulfone and [beta Ala(8)]neurokinin A- (4-10), respectively) in producing contraction of the circular muscle of the guinea-pig proximal colon. [Sar(9)]Substance P sulfone produced a marked depolarization, action potentials and increase in membrane c onductance. On the other hand, [beta Ala(8)]neurokinin A-(4-10) produc ed less depolarization of the cell membrane and did not change membran e resistance. Nifedipine (1 mu M) greatly reduced (80% inhibition) the contraction due to [Sar(9)]substance P sulfone while that due to [bet a Ala(8)]neurokinin A-(4-10) was slightly affected (13% inhibition). A ction potentials induced by either agonist were suppressed by nifedipi ne, while depolarization was reduced only to a minor extent. When test ed in a Ca2+-free medium, the contraction produced by either agonist w as greatly reduced (84-89%) as compared to the control. In organ bath experiments [Sar(9)]substance P sulfone and [beta Ala(8)]neurokinin A- (4-10) produced concentration-dependent contraction of the circular mu scle of the colon (EC(50)8 and 12 nM, respectively). Nifedipine (1 mu M) markedly suppressed the response to [Sar(9)]substance P sulfone whi le that to [beta Ala(8)]neurokinin A-(4-10) was only slightly depresse d. These findings demonstrate that NK1 receptor-mediated contraction i s strictly linked to membrane depolarization and action potentials gen eration through nifedipine-sensitive Ca2+ channels (electromechanical coupling) while the NK2 receptor-mediated contraction is substantially unrelated to depolarization and, while being largely dependent upon e xtracellular Ca2+, is nifedipine-resistant, possibly linked to the ope ning of non-selective (Ca2+-permeable) receptor-gated cation channels (pharmacomechanical coupling).