Inhibitory effects of procaine on the contractile responses of the guinea-pig Taenia caecum to acetylcholine, substance P and potassium chloride

1984 ◽  
Vol 326 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Takeo Ishii ◽  
Yasuo Shimo
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Potassium Chloride ◽  
Inhibitory Effects ◽  
Contractile Responses

Beta 2-adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro

1993 ◽  
Vol 74 (3) ◽  
pp. 1195-1199 ◽  
Author(s):  
G. M. Verleden ◽  
M. G. Belvisi ◽  
K. F. Rabe ◽  
M. Miura ◽  
P. J. Barnes
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Sensory Nerves ◽  
Inhibitory Effects ◽  
Exogenous Substance ◽  
Dependent Inhibition ◽  
Adrenoceptor Agonists ◽  
Beta 2

Nonadrenergic noncholinergic (NANC) contractile responses in guinea pig bronchi are due to the release of tachykinins from airway sensory nerves. The purpose of this study was to determine whether beta 2-receptor agonists modulate NANC contractions in guinea pig bronchi in vitro. Bronchial rings were suspended in organ baths for isometric measurement of tension, and comparable contractions were induced by electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) or by exogenous substance P (3 microM). Aformoterol and salbutamol produced concentration-dependent inhibition of the NANC contraction, with aformoterol being ninefold more potent than salbutamol; approximate 50% inhibitory concentrations for aformoterol and salbutamol were 1.03 nM (n = 6) and 9.3 nM (n = 6), respectively. Aformoterol also inhibited the contraction induced by exogenous substance P but to a far lesser extent than its inhibition of EFS-induced responses. The inhibitory effects of formoterol (10 nM) on responses to EFS at 8 Hz were significantly prevented by propranolol (1 microM) and ICI 118551 (a beta 2-antagonist, 0.1 microM) but not by atenolol (a beta 1-antagonist, 1 microM) or phentolamine (10 microM). These experiments demonstrate that beta 2-agonists may modulate the release of tachykinins from airway sensory nerves by prejunctional receptors.

Erenumab (AMG 334), a monoclonal antagonist antibody against the canonical CGRP receptor, does not impair vasodilatory or contractile responses to other vasoactive agents in human isolated cranial arteries

Cephalalgia ◽  
2019 ◽  
Vol 39 (14) ◽  
pp. 1745-1752 ◽  
Author(s):  
Lena Ohlsson ◽  
Kristian A Haanes ◽  
Erik Kronvall ◽  
Cen Xu ◽  
Josefin Snellman ◽  
...  
Keyword(s):  
Substance P ◽  
Potassium Chloride ◽  
Human Monoclonal Antibody ◽  
Calcitonin Gene Related Peptide ◽  
Contractile Responses ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Meningeal Arteries ◽  
Per Se ◽  
Cranial Arteries

Background Calcitonin gene-related peptide (CGRP) is a neuronal transmitter present in intracranial sensory nerves, where it is involved in migraine pathophysiology as well as other biological functions. Recently, the fully human monoclonal antibody erenumab (AMG 334), which targets the canonical calcitonin gene-related peptide receptor, showed significant prophylactic efficacy and favourable safety in phase II and III clinical trials for episodic and chronic migraine and is now approved for migraine prevention in several countries. Objective Given that calcitonin gene-related peptide can mediate vasodilation, we investigated the effect of erenumab on vasoactive responses in the presence or absence of various vasodilatory and vasocontractile mediators in a model using isolated human cerebral and meningeal arteries. Methods Ring segments of human isolated cerebral and meningeal arteries were mounted in a sensitive myograph. On arterial segments pre-contracted with 30 mM potassium chloride, vasoactive responses to calcitonin gene-related peptide were studied in the presence of different concentrations of erenumab. At the maximal tested inhibitory concentration of erenumab (100 nM), functional arterial relaxation in response to nicardipine or substance P, and the contractile responses to sumatriptan and dihydroergotamine were examined. Results 30 mM potassium chloride produced a stable contraction of the vessel segments and calcitonin gene-related peptide induced a concentration-dependent relaxation. We observed that (i) erenumab had no direct contractile or relaxant effects per se (by itself), (ii) pre-treatment with erenumab antagonized the calcitonin gene-related peptide-induced relaxation in a competitive manner, (iii) the relaxant responses to nicardipine or substance P were unaffected in the presence of erenumab and (iv) the contraction induced by sumatriptan or dihydroergotamine was not modified by erenumab. Conclusion Our findings demonstrate that erenumab, while not associated with vasoactive properties per se, specifically inhibits calcitonin gene-related peptide-induced relaxation of cranial arteries without impacting vasodilatory responses or contractile responses of endogenous or pharmacological vasoactive compounds.

Dual effects of PACAP on guinea pig gallbladder muscle via PACAP-preferring and VIP/PACAP-preferring receptors

1997 ◽  
Vol 272 (6) ◽  
pp. G1433-G1438 ◽  
Author(s):  
H. P. Parkman ◽  
A. P. Pagano ◽  
J. P. Ryan
Keyword(s):  
Substance P ◽  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Direct Action ◽  
Inhibitory Effects ◽  
Relaxant Effect ◽  
Pituitary Adenylate Cyclase ◽  
Substance P Receptor ◽  
Dose Dependent

The aims of this study were to determine the effect and mechanism of action of pituitary adenylate cyclase-activating peptide (PACAP) on gallbladder muscle. Guinea pig gallbladder muscle strips were studied isometrically. In noncontracted muscle strips, PACAP-27 and PACAP-38 caused dose-dependent contractions, whereas vasoactive intestinal peptide (VIP) caused dose-dependent relaxation. PACAP-27 contractions were resistant to tetrodotoxin, atropine, and the substance P receptor antagonist [D-Arg1,D-Trp7,9,Leu11]substance P (Spantide) but were inhibited by the selective PACAP receptor antagonist PACAP-(6-38) and slightly increased with the VIP receptor antagonist [4-chloro-D-Phe6,Leu17]VIP. In cholecystokinin-precontracted muscle strips, both VIP and PACAP caused relaxations. This relaxant effect of PACAP-27 was inhibited by PACAP-(6-38) and [4-chloro-D-Phe6,Leu17]VIP, but not by tetrodotoxin. These studies suggest that PACAP has dual excitatory and inhibitory effects on guinea pig gallbladder muscle. The contractile effect of PACAP is a direct action on muscle through PACAP-preferring receptors. The relaxant effect of PACAP is seen in precontracted muscle strips and mediated through VIP/ PACAP-preferring receptors.

Sign in / Sign up

Export Citation Format

Share Document