Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi

Santicioli, Paolo; Meini, Stefania; Giuliani, Sandro; Lecci, Alessandro; Maggi, Carlo Alberto

doi:10.1016/j.ejphar.2013.10.029

Cited by 3 publications

(4 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results proved that midcervical vagotomy eliminated bi‐phasic respiratory rate response, and augmentation of tidal volume, while supranodosal section of the vagi abrogated drop in tidal volume, residual after midcrevical vagotomy. NK 2 receptors were shown to be distributed throughout the human bronchi and animal bronchial smooth muscles and epithelium . Activation of those localized in airway smooth muscles in in vitro condition, thus unbiased by the vagal loop, caused direct bronchoconstriction …”

Section: Discussionmentioning

confidence: 98%

“…NK 2 receptors were shown to be distributed throughout the human bronchi and animal bronchial smooth muscles and epithelium . Activation of those localized in airway smooth muscles in in vitro condition, thus unbiased by the vagal loop, caused direct bronchoconstriction …”

Section: Discussionmentioning

confidence: 98%

“…NK 2 receptors were shown to be distributed throughout the human bronchi and animal bronchial smooth muscles and epithelium. [23][24][25][26] Activation of those localized in airway smooth muscles in in vitro condition, thus unbiased by the vagal loop, caused direct bronchoconstriction. 25,26 In our study, respiratory effects of NKA disappeared after vagotomy, thus they were vagally mediated, presumably via stimulation of NK 2 receptors associated with the vagus nerve afferents.…”

Section: Discussionmentioning

confidence: 99%

“…[23][24][25][26] Activation of those localized in airway smooth muscles in in vitro condition, thus unbiased by the vagal loop, caused direct bronchoconstriction. 25,26 In our study, respiratory effects of NKA disappeared after vagotomy, thus they were vagally mediated, presumably via stimulation of NK 2 receptors associated with the vagus nerve afferents. This is 27 The RARs, stimulated by mechanical, chemical and nociceptive stimuli are responsible for the neural airway defense reflexes involving mucus secretion, bronchoconstriction and changes in ventilatory pattern.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

The role of vagal pathway andNK₁andNK₂receptors in cardiovascular and respiratory effects of neurokinin A

Kaczyńska

Jampolska

Szereda-Przestaszewska

2016

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Neurokinin A (NKA) is a peptide neurotransmitter that participates in the regulation of breathing and the cardiovascular system. The purpose of the current study was to determine the cardiorespiratory pattern exerted by the systemic injection of NKA, to look at the contribution of neurokinin NK1 and NK2 receptors, and to establish the engagement of the vagal pathway in mediation of these responses. The effects of intravenous injections of NKA (50 μg/kg) were studied in anaesthetized, spontaneously breathing rats in the following experimental schemes: in neurally intact rats; and vagotomized at either midcervical or supranodosal level. Intravenous injections of NKA in the intact rats evoked sudden and short-lived increase in the respiratory rate concomitant with drop in tidal volume, followed by a prolonged depression, coupled with continuous augmentation of the tidal volume. Respiratory alterations were accompanied by transient tachycardia and prolonged hypotension. Midcervical vagotomy eliminated respiratory rate response and augmentation of tidal volume. Section of supranodosal vagi abrogated all respiratory reactions. NK2 receptor blockade abolished respiratory changes without affecting cardiovascular effects, whereas NK1 receptor blockade significantly reduced hypotension and increase in heart rate with no impact on the respiratory system. These results indicate that NKA induced changes in the breathing resulting from an excitation of the NK2 receptors on the vagal endings. A fall in blood pressure triggered by NKA occurs outside of the vagus nerve and is probably mediated via its direct action on vascular smooth muscles supplied with NK1 receptors.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The role of vagal pathway andNK₁andNK₂receptors in cardiovascular and respiratory effects of neurokinin A

Kaczyńska

Jampolska

Szereda-Przestaszewska

2016

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

The role of melatonin, neurokinin, neurotrophic tyrosine kinase and glucocorticoid receptors in antidepressant-like effect

Pytka

Młyniec

Podkowa

et al. 2017

Pharmacological Reports

View full text Add to dashboard Cite

Over the last few decades, depression has become one of the major public health problems in our society. This problem is connected not only with morbidity, but also with treatment, specifically with the effectiveness of the therapy as well as the concomitant side effects of available antidepressants. Major depressive disorder is a complex clinical entity, including different molecular mechanisms and neurological processes. This complexity is a challenge for scientists seeking to discover an innovatory antidepressant drug with multiple and complementary mechanisms of action. In this review, we discuss the role of melatonin, neurokinin, neurotrophic tyrosine kinase and glucocorticoid receptors in depression and antidepressant-like effects.

show abstract

The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications

Gadais

Ballet

2020

CMC

View full text Add to dashboard Cite

The neurokinins are indisputably essential neurotransmitters in numerous patho- and physiological events. Being widely distributed in the central nervous system (CNS) and peripheral tissues, their discovery rapidly promoted them to drugs targets. A necessity for molecular tools to understand the biological role of this class endogenous peptides and their receptors prompted the scientific community to design ligands displaying either agonist and antagonist activity at the three main neurokinin receptors, called NK1, NK2 and NK3. Several strategies were implemented for this purpose. With a preference for small non-peptidic ligands, many research groups invested efforts in synthesizing and evaluating a wide range of scaffolds, but only the NK1 antagonist Aprepitant (EMENDT) and its prodrug Fosaprepitant (IVEMENDT) have been approved by the Food Drug Administration (FDA) for the treatment of Chemotherapy-Induced and Post-Operative Nausea and Vomiting (CINV and PONV, respectively). While non-peptidic drugs showed limitations, especially in side effect control, peptidic and pseudopeptidic compounds progressively regained attention. Various strategies were implemented to modulate affinity, selectivity and activity of the newly designed ligands. Replacement of canonical amino acids, incorporation of conformational constraints, and fusion with non-peptidic moieties gave rise to families of ligands displaying individual or dual NK1, NK2 and NK3 antagonism, that ultimately was combined with non-neurokinin ligands (such as opioids) to target enhanced biological impact.

show abstract

Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi

Cited by 3 publications

References 51 publications

The role of vagal pathway andNK₁andNK₂receptors in cardiovascular and respiratory effects of neurokinin A

The role of vagal pathway andNK₁andNK₂receptors in cardiovascular and respiratory effects of neurokinin A

The role of melatonin, neurokinin, neurotrophic tyrosine kinase and glucocorticoid receptors in antidepressant-like effect

The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications

Contact Info

Product

Resources

About

Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi

Cited by 3 publications

References 51 publications

The role of vagal pathway andNK1andNK2receptors in cardiovascular and respiratory effects of neurokinin A

The role of vagal pathway andNK1andNK2receptors in cardiovascular and respiratory effects of neurokinin A

The role of melatonin, neurokinin, neurotrophic tyrosine kinase and glucocorticoid receptors in antidepressant-like effect

The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications

Contact Info

Product

Resources

About

The role of vagal pathway andNK₁andNK₂receptors in cardiovascular and respiratory effects of neurokinin A

The role of vagal pathway andNK₁andNK₂receptors in cardiovascular and respiratory effects of neurokinin A