DIFFERENTIAL SENSITIVITY TO BRADYKININ OF ESOPHAGEAL DISTENSION SENSITIVE MECHANORECEPTORS IN VAGAL AND SYMPATHETIC AFFERENTS OF THE OPOSSUM

被引:59
作者
SENGUPTA, JN
SAHA, JK
GOYAL, RK
机构
[1] CHARLES A DANA RES INST, CTR SWALLOWING & MOTIL DISORDERS, BOSTON, MA 02215 USA
[2] HARVARD UNIV, SCH MED,BETH ISRAEL HOSP,THORNDIKE LAB,DEPT MED, DIV GASTROENTEROL, BOSTON, MA 02115 USA
关键词
D O I
10.1152/jn.1992.68.4.1053
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Single-unit activity was recorded from afferent fibers in the cervical vagus and thoracic sympathetic nerves in the opossum. Seventy-six fibers that responded to balloon distension (100 mmHg for 10 s) of the smooth muscle portion of the esophagus were selected for futher study. 2. Forty-nine distension-sensitive afferents were identified in the vagus nerve. The stimulus respnse function (SRF) of 41 fibers behaved as "low-threshold mechanoreceptors" (LTM), with mean threshold value of 0.29 +/- 0.17 mmHg and saturation pressure of 50-70 mmHg. All fibers demonstrated background activity, with a mean rate of 8.83 +/- 0.93 imp/s (range 0.5-31.25). 3. Twenty-seven distension-sensitive afferents were identified in teh thoracic sympathetic chain (T6-t8) and splanchnic nerve. The SRF study revealed two types of fibers: 1) a wide-dynamic-range mechanonociceptor (WDRMN) with a mean response threshold of 3.43 +/- 0.90 mmH (n = 15) and 2) a "high-threshol mechanonociceptor" (HTMN) with a mean response threshold of 34.93 +/- 2.70 mmHg (n = 12). The mean background activities of WDRMN and HTMN fibers were 0.5 +/- 0.13 and 0.20 +/- 0.08 imp/s, respectively. Both of these fibers had saturation pressures of > 120 mmHg. 4. The conduction velocities were measured in 14 LTM, 10 WDRMN, and seven HTMN fibers. The mean conduction velocity of LTM fibers was 5.03 +/- 1.35 m/s (range 0.97-18.00), with five unmyelinated "C"-fibers (<2.5 m/s) and nine A-delta fibers (>2.5 m/s. The mean conduction velocity of WDRMN fibers was 3.64 +/- 0.84 m/s (range 1.10-8.25), consisting fo five C-fibers and five A-delta fibers. The mean conduction velocity of HTMN fibers was 6.22 +/- 2.35 m/s (range 1.73-24.66); three fibers were unmyelinated C-fibers, and four fibers were A-delta fibers. 5. The sensitivity to bradykinin (BK) administereed systemically (1-300 mug/kg) was tested in LTM (n = 34), WDRMN (n = 15), and HTMN (n = 8) fibers. Twenty-six (66%) LTM fibers responded to BK, and eight (34%) fibers were insensitive to BK. All 15 WDRMN and eight HTMN fibers tested responded to BK. 6. Tachyphylaxis to repeated application of BK was tested in all three classed of fibers. The vagal LTM fibers did not exhibit tachyphylaxis when BK was given at an ntervals of 10 min. the sympathetic WDRMN and HTMN fibers demonstrated partial tachyphylaxis when BK was injected at 10-min intervals, but not when BK was injected at 20-min intervals. 7. Dose-response curves to BK were constructed by giving 1-300 mug/kg of BK in an ascending series of doses at 20-min intervals. All BK-responsive fibers tested exhibited dose-dependent increase in discharge rate. 8. The mean maximum response of LTM fibers to BK, 17.52 +/-3.48 imp/s, was only 33% of mean maximum respense to 70-mmHg balloon distension (53.36 +/- 4.10 imp/s, n = 26). The mean maximum response of WDRMN fibers to BK, 7.94 +/- 1.64 imp/s, was 80% of their maximum response to balloon distension (9.89 +/- 1.62 imp/s, n = 15). The mean maximum response of HTMN fibers to BK 14.45 +/- 3.88 imp/s, was 134% of their maximum response to balloon distension (10.76 +/- 1.62 imp/s, n = 8). 9. In four LTM fibers, responses to carbachol (1-30 mug/kg) and BK (1-100 mug/kg) were compared. Carbachol produced more activity of LTM compared with BK. Carbachol also caused greater contraction of longitudinal muscle than BK. 10. A number of synthetic analogues of BK was tested for their agonistic and antagonistic activities to identify BK receptor subtypes involved in actiation of the three types of fibers. [D-Phe7]-BK (100 mug/kg) and [Thi5,8D-Phe7]-BK (100 mug/kg) exhibited agonist but no antagonist activity on LTM fibers or esophageal muscle contraction (n = 6 for each analogue). These two analogues, however, exhibited anatagonist effects in WDRMN fibers (n = 3 for each analogue) without showing any agonistic activity. In WDRMN fibers, [D-Phe7]-BK and [Thi5,8D-Phe7]-BK produced 51% (P < 0.05) and 26% (P < 0.5) inhibition of responses to BK, respectively. Both analogues also produced inhibition of response to BK in on HTMN fiber tested. On the other hand, [des-Arg9, Leu8]-BK (100 mug/kg), a B1 receptor antagonist, produced on inhibition of respnse of LTM (n = 2) and WDRMN (n = 2) fibers to BK. Similarily, Lys-Lys-[Hyp3Thi5,8D-Phe7]-BK (100 mug/kg) was also found inactive in blocking respnses of LTM (n = 3) and HTMN (n = 4) fibers tested to BK. 11. The study suggestes that 1) responses of vagal LTM fibers to BK were secondary to longitudinal muscle contraction produced by postjunctional B4 receptor activation and 2) response in sympathetic WDRMN and HTMN fibers to BK was a direct action through a B2 receptor subtype of the fiber endings.
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页码:1053 / 1067
页数:15
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