ISSN:
1432-1912
Keywords:
Intestinal smooth muscle
;
Contraction
;
Intracellular signalling
;
Desensitization
;
Substance P
;
Histamine
;
Phorbol-12,13-dibutyrate
;
Polymyxin B
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary (1) This study investigated a possible involvement of protein kinase C (PKC) in the substance P-induced contraction of the longitudinal muscle of the guinea-pig isolated ileum. (2) The predominant effect of the PKC activator, phorbol-12,13-dibutyrate (PDB), was to change the time course of the response to substance P. While the initial peak contraction was hardly influenced by PDB, the fading of the contraction was accelerated to an extent that any tonic contraction which normally followed the initial peak response was prevented. This inhibitory effect of PDB on the tonic contraction was immediate in onset and related to its concentration (20–200 nM); responses to half-maximally (2–7 nM) or maximally effective (0.74 μM) concentrations of substance P were affected in the same manner. Tetrodotoxin (0.6 μM) did not alter the effect of PDB. Phorbol-13-monoacetate (2 μM), a phorbol ester which does not stimulate PKC, failed to change the time course of the substance P-induced contraction. (3) The tonic component of half-maximal contractile responses to histamine (0.20.4 μM) was also depressed by PDB (0.2 μM) whereas the tonic component of maximal responses to histamine (9 μM) was enhanced. (4) PDB (0.2 μM) reduced desensitization to substance P as judged by the reduction of the peak response to substance P (2–7 nM) following a 10-min exposure to a high concentration of the pepide (0.74μM). (5) The PKC inhibitor, polymyxin B (0.1–0.3 mM), reduced the peak contractile response to substance P, slowed the fading of the contraction, and antagonized the inhibitory effect of PDB on the tonic contraction. (6) These findings suggest that, in intestinal smooth muscle, the phasic and tonic components of receptor-mediated contractions involve separate signalling mechanisms. The tonic component of contraction appears to be under the control of protein kinase C which determines whether the contraction fades away or is sustained. Fading of the substance P- induced contraction does not seem to reflect desensitization of the muscle to this agonist.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00165146
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