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
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).