Holzer P, Lippe I T
University of Graz, Department of Experimental and Clinical Pharmacology, Austria.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):214-20. doi: 10.1007/BF00165146.
(1) The 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 microM) concentrations of substance P were affected in the same manner. Tetrodotoxin (0.6 microM) did not alter the effect of PDB. Phorbol-13-monoacetate (2 microM), 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 (0.2-0.4 microM) was also depressed by PDB (0.2 microM) whereas the tonic component of maximal responses to histamine (9 microM) was enhanced. (4) PDB (0.2 microM) 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 peptide (0.74 microM). (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.(ABSTRACT TRUNCATED AT 250 WORDS)
(1) 本研究调查了蛋白激酶C（PKC）是否可能参与P物质诱导的豚鼠离体回肠纵肌收缩。(2) PKC激活剂佛波醇-12,13-二丁酸酯（PDB）的主要作用是改变对P物质反应的时间进程。虽然初始峰值收缩几乎不受PDB影响，但收缩的消退加速到足以阻止通常在初始峰值反应后出现的任何强直收缩的程度。PDB对强直收缩的这种抑制作用起效迅速且与其浓度（20 - 200 nM）相关；对半数最大有效浓度（2 - 7 nM）或最大有效浓度（0.74 μM）的P物质的反应受到同样影响。河豚毒素（0.6 μM）未改变PDB的作用。佛波醇-13-单乙酸酯（2 μM），一种不刺激PKC的佛波醇酯，未能改变P物质诱导的收缩的时间进程。(3) PDB（0.2 μM）也使对组胺（0.2 - 0.4 μM）的半数最大收缩反应的强直成分受到抑制，而对组胺（9 μM）的最大反应的强直成分则增强。(4) 根据在10分钟暴露于高浓度肽（0.74 μM）后对P物质（2 - 7 nM）的峰值反应的降低判断，PDB（0.2 μM）减少了对P物质的脱敏。(5) PKC抑制剂多粘菌素B（0.1 - 0.3 mM）降低了对P物质的峰值收缩反应，减缓了收缩的消退，并拮抗了PDB对强直收缩的抑制作用。（摘要截选至250字）
