一氧化氮对大鼠近端结肠自发机械活动的调节作用

Modulation by nitric oxide of spontaneous mechanical activity in rat proximal colon.

Mulè F, D'Angelo S, Amato A, Contino I, Serio R

Dipartimento di Biologia Cellulare e dello Sviluppo, Università degli Studi di Palermo, Italy.

J Auton Pharmacol. 1999 Feb;19(1):1-6. doi: 10.1046/j.1365-2680.1999.00108.x.

Abstract

In order to examine the role of nitric oxide (NO) in the tonic neural inhibition in rat proximal colon, the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) were studied on the spontaneous contractions of circular muscle (monitored as intraluminal pressure changes) and of longitudinal muscle (detected as isometric tension changes). 2. L-NAME (3 x 10(-6)-3 x 10(-4) M) caused a concentration-dependent increase in the amplitude of circular contractions, without affecting those of longitudinal muscle. This effect was prevented by L-arginine (1-5 x 10(-3) M), but not D-arginine. 3. In the presence of tetrodotoxin (10(-6) M), which per se induced increase of the pressure waves, L-NAME (10(-4) M) caused no further effects on the amplitude of the spontaneous contractions. 4. The response to L-NAME (10(-4) M) was unaffected by atropine (10(-6) M), guanethidine (10(-6) M), hexamethonium (up to 3 x 10(-4) M) or alpha-chymotrypsin (up to 5 U ml(-1)). 5. NK2 receptor antagonists, SR 48968 (3 x 10(-6) M) or MEN 10627 (10(-6) M), produced a reduction of the amplitude of the pressure waves but failed to affect the contractile response to L-NAME (10(-4) M). 6. These findings suggest that tonic production of NO from inhibitory neurones influences the degree of contractions of circular muscle. An involvement of an inhibitory peptide as well as disinhibition of cholinergic or NK2-tachykinergic excitatory neurotransmission in the mechanism of NO action can be ruled out.

摘要

为研究一氧化氮（NO）在大鼠近端结肠紧张性神经抑制中的作用，研究了N（ω）-硝基-L-精氨酸甲酯（L-NAME）对环行肌自发收缩（以内腔压力变化监测）和纵行肌自发收缩（以等长张力变化检测）的影响。2. L-NAME（3×10⁻⁶ - 3×10⁻⁴ M）引起环行收缩幅度呈浓度依赖性增加，而不影响纵行肌收缩幅度。L-精氨酸（1 - 5×10⁻³ M）可阻断此效应，而D-精氨酸则不能。3. 在存在河豚毒素（10⁻⁶ M）的情况下，河豚毒素本身可诱导压力波增加，L-NAME（10⁻⁴ M）对自发收缩幅度无进一步影响。4. 对L-NAME（10⁻⁴ M）的反应不受阿托品（10⁻⁶ M）、胍乙啶（10⁻⁶ M）、六甲铵（高达3×10⁻⁴ M）或α-糜蛋白酶（高达5 U ml⁻¹）的影响。5. NK2受体拮抗剂SR 48968（3×10⁻⁶ M）或MEN 10627（10⁻⁶ M）可使压力波幅度降低，但未能影响对L-NAME（10⁻⁴ M）的收缩反应。6. 这些发现表明，抑制性神经元产生的NO张力影响环行肌的收缩程度。可以排除抑制性肽以及胆碱能或NK2-速激肽能兴奋性神经传递去抑制参与NO作用机制的可能性。