Action of the newly discovered mammalian tachykinins, substance K and neuromedin K, on gastroduodenal motility of anesthetized dogs

doi:10.1016/0167-0115(87)90065-6

Regulatory Peptides

Volume 17, Issue 4, April 1987, Pages 221-228

https://doi.org/10.1016/0167-0115(87)90065-6 Get rights and content

Abstract

The present experiments examined the local effects of two new mammalian tachykinins isolated from porcine spinal cord, substance K and neuromedin K, on gastroduodenal motility of anesthetized dogs. Tachykinins were injected through the gastroepiploic and cranial pancreaticoduodenal arteries at concentrations ranging from 1 to 100 ng/ml. Substance K, neuromedin K and substance P increased gastroduodenal smooth muscle contractions in a dose-dependent manner. The contractile response of the gastric antrum to newly discovered tachykinins was not as longlasting as that to substance P. The potencies of various tachykinins on contractile responses showed the following rank order of potencies: $physalaemin = eledoisin = substance P > substance K = neuromedin K$ in gastric smooth muscle; $physalaemin = substance P = eledoisin > substance K = neuromedin K$ in the duodenal smooth muscle. Administration of atropine (100–200 μg/kg) inhibited the effect of tachykinins both in the gastric antrum and in the proximal duodenum. These results indicate that substance K and neuromedin K could act as transmitters or as modulators of neuronal activity influencing gastroduodenal motility.

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Cited by (10)

Role of tachykininergic and cholinergic pathways in modulating canine gastric tone and compliance in vivo
2002, Pharmacological Research
Acetylcholine and tachykinins act as co-transmitters along excitatory pathways at different gut levels. Since cholinergic pathways are involved in maintaining gastric tone during fasting, our aim was to study the possible role of tachykininergic pathways in modulating canine gastric tone and compliance in vivo by using selective tachykinin receptor antagonists. In four fasting, conscious dogs, we characterized the pressure–volume relationship in the proximal stomach by using a barostat. We increased the pressure of the intragastric bag by 2 mmHg increments every 3 min, starting from a baseline value of 2 up to 12 mmHg. Drug effects were investigated by studying pressure–volume relationships before and 15 min after intravenous (i.v.) administration of SR140333, SR48968, or SR142801 (respectively, NK ₁-, NK₂ -, and NK ₃-receptor antagonist, each at the dose of 1 mg kg ⁻¹) or atropine (100μ g kg ⁻¹). Pressure–volume curves were fitted by nonlinear regression analysis. Before drug administration, the curve that best fitted the pressure–volume relationship was exponential. SR140333, SR48968 and SR142801 did not affect baseline gastric tone or the gastric pressure–volume curve at any distension level. At a distending pressure of 6 mmHg, the Δ volumes obtained after administration of SR140333, SR48968 or SR142801 vs control were 65 ± 28, 27 ± 26, 14 ± 20 ml, respectively. The same was true even when all three antagonists were administered together to achieve simultaneous blockade of all three tachykinin receptor subtypes. Atropine increased baseline gastric volume ( Δ volume = 237 ± 15 ml; P< 0.01) and significantly (P < 0.0001) shifted the pressure–volume curve to the left. After atropine, a linear equation best fitted the pressure–volume curve. We conclude that tachykininergic pathways are not involved in modulating canine gastric tone and compliance during fasting, whereas cholinergic pathways play a major role not only in maintaining gastric tone, but also in modulating the compliance of the proximal stomach to a distending stimulus.
Tachykinins in the gut. Part I. Expression, release and motor function
1997, Pharmacology and Therapeutics
The preprotachykinin-A gene-derived peptides substance P and neurokinin (NK) A are expressed in distinct neural pathways of the mammalian gut. When released from intrinsic enteric or extrinsic primary afferent neurons, tachykinins have the potential to influence both nerve and muscle by way of interaction with three different types of tachykinin receptor, termed NK₁, NK₂ and NK₃ receptors. Most prominent among the effects of tachykinins is their excitatory action on gastrointestinal motor activity, which is seen in virtually all regions and layers of the mammalian gut. This action depends not only on a direct activation of the muscle through NK₁ and/or NK₂ receptors, but also on stimulation of excitatory enteric motor pathways through NK₃ and/or NK₁ receptors. In addition, tachykinins can inhibit motor activity by stimulating either inhibitory neuronal pathways or interrupting excitatory rekys. A synopsis of the available data indicates that endogenous substance P and NKA interact with other enteric transmitters in the physiological control of gastrointestinal motor activity. Derangement of the regulatory roles of tachykinins may be a factor in the gastrointestinal dysmotility associated with infection, inflammation, stress and pain. In a therapeutic perspective, it would seem conceivable, therefore, that tachykinin agonists and antagonists are adjuncts to the treatment of motor disorders that involve pathological disturbances of the gastrointestinal tachykinin system.
Tachykinin receptors in gastrointestinal motility
1995, Regulatory Peptides
Distribution of neurokinin A-like and neurokinin B-like immunoreactivity in human peripheral tissues
1991, Regulatory Peptides
Using specific radioimmunoassay and immunocytochemistry for neurokinin A (NKA) and neurokinin B (NKB), distribution and localization of the two peptides in human peripheral tissues were studied. Both NKA-like immunoreactivity (NKA-LI) and NKB-like immunoreactivity (NKB-LI) were present in the walls of the gut and gall bladder and in the pancreas. In the gut, the values for NKA-LI were 0.56–35.73 pmol/g wet weight, while those in pancreas and gall bladder were 0.64–0.68 and 0.36 pmol/g wet weight, respectively. The values of NKB-LI were 0.45–2.66 pmol/g wet weight in the gut, 0.93–1.65 pmol/g wet weight in the pancreas, and 0.30 pmol/g wet weight in the gall bladder. The immunocytochemical reactivity to both peptides was localized to ganglia of the submucosal and myenteric nerve plexuses in the gut wall, and to neurons in the muscle layer and mucosa of the gut wall. Weak but positive NKA-LI appeared in nerve cells of the pancreas, while NKB-LI was not detectable in the pancreas. Conversely, in the gall bladder wall, NKA-LI was undetectable while a very faint NKB-LI was found in the muscle layer. The localization of NKA corresponded closely to that of NKB in the tissues although the relative concentrations of the peptides varied from organ to organ.
Distribution and localization of neurokinin A-like immunoreactivity and neurokinin B-like immunoreactivity in rat peripheral tissue
1990, Regulatory Peptides
Using specific radioimmunoassays and immunocytochemistry for neurokinin A (NKA) and neurokinin B (NKB), distribution and localization of these peptides in rat peripheral tissues were studied. NKA-like immunoreactivity (NKA-LI) was present in highest levels of 15.7–23.9 pmol/g wet wt. and NKB-like immunoreactivity (NKB-LI) was in levels of 0.33–0.67 pmol/g wet wt., throughout the gastrointestinal tract involving stomach, duodenum, jejunum, ileum and colon. Immunocytochemical analysis of gastrointestinal tract revealed that NKA-LI and NKB-LI localized in ganglia of both the submucosal and myenteric plexuses as well as varicose neurons in the mucosa and the muscle layer of the small and large intestine. On the other hand, high levels of NKB-LI were observed in oesophagus (0.83 ± 0.08 pmol/g wet wt.), adrenal (1.02 ± 0.21), head of pancreas (0.73 ± 0.06) and kidney (0.98 ± 0.05).
The present study shows the difference of localization of NKA-LI and NKB-LI in peripheral tissues and suggests that NKB may have some physiological role differing from that of NKA in peripheral tissues.
Duodenal SP-like immunoreactivity is decreased in experimentally-induced duodenal ulcers
1990, Neuroscience Letters
Substance P-like immunoreactivity (SP-li) is decreased in duodenal samples of animals treated with a single dose of an ulcerogen such as dulcerozine, mepirizole or cysteamine. Unlike dulcerozine- or mepirizole-induced ulcers the degree of cysteamine-induced duodenal lesions is inversely correlated with the levels of duodenal SP-li. A significant decrease in duodenal SP-li was observed at 24 h, but not at 6 h after a single oral dose of cysteamine. These findings show that endogenous SP may play an importal local role in duodenal ulcerogenesis.

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^∗: Present address: Department of Physiology, Graves Hall, 333 West 10th Avenue, College of Medicine, The Ohio State University, Columbus, OH 43210-1238, U.S.A.

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Action of the newly discovered mammalian tachykinins, substance K and neuromedin K, on gastroduodenal motility of anesthetized dogs

Abstract

Trends Neurosci.

Neuroscience

Eur. J. Pharmacol.

Neurosci. Res.

Life Sci.

Gastroenterology

Regul. Peptides

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Neuroscience

Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord

Biochem. Biophys. Res. Commun.