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At least 451 records · Page 25Linked to original sources
PubMed1986

Relaxant profile of synthetic atrial natriuretic factor on guinea-pig pulmonary tissues.

Synthetic atrial natriuretic factor (ANF) (3.22 X 10(-7)-9.67 X 10(-9) M) produced relaxation of the intrinsic and extrinsic tone of the guinea-pig trachea. ANF was more potent on the trachea as compared to the parenchyma of the guinea-pig. On the trachea ANF was a more potent relaxant of intrinsic tonus or contractions induced by methacholine as compared to contractions induced by leukotriene D4. When administered by aerosol to anesthetized spontaneously breathing guinea-pigs, ANF produced neither bronchodilation nor inhibition of bronchoconstriction induced by an aerosol of leukotriene D4.

Airway Resistance↗
PubMed1986

Agonist-induced contractile responses of human bronchial muscle in vitro: effects of Ca2+ removal, La3+ and PY108068.

The effects of reducing the extracellular Ca2+ concentration ([Ca2+]0), the effects of La3+ and the dihydropyridine Ca2+ entry blocker PY108068 on contractile responses in human isolated bronchial strips have been compared. Reducing [Ca2+]0 or the presence of La3+ (1 mM) caused a reduction in basal tone, whereas PY108068 (1 microM) had no effect on unstimulated preparations. Response to KCl and A23187 were, in general, more markedly depressed by reducing the entry of extracellular Ca2+, with La3+ or PY108068 than were those to histamine, methacholine and LTD4. The effects of reducing [Ca2+]0, La3+ and PY108068 on responses to the receptor-mediated agents suggest that intracellular Ca2+ may be mobilized upon receptor activation, whereas responses to KCl and A23187 appear to be dependent upon the influx of extracellular Ca2+. More than one source of activator Ca2+ can therefore be involved in the development of contractions in human airway smooth muscle. These findings are in accord with those observed for in vitro airways preparations from experimental animals.

Bronchi↗
PubMed1986

Muscarinic stimulation of prostacyclin synthesis by the rat penis.

An in vitro model for the investigation of PGI2 synthesis by the rat penis is described. Acetyl-beta-methylcholine (methacholine; MeCh) and carbamyl choline (carbachol) stimulated PGI2 synthesis in a dose-dependent manner (ED50 = 1.5 X 10(-6); 2.5 X 10(-6), respectively), whereas adrenaline, noradrenaline, histamine, serotonin, vasoactive intestinal polypeptide (VIP), nicotine, dimethyl phenylpiperazinium (DMPP) and adenosine triphosphate (ATP) were without effect. MeCh (10(-6) mol/l)- and carbachol (10(-6) mol/l)-stimulated PGI2 synthesis was inhibited by atropine in a dose-dependent manner (ID50 = 2.5 X 10(-7) mol/l; 7 X 10(-6) mol/l, respectively). The inhibition by atropine of MeCh-stimulated PGI2 synthesis was competitive. MeCh (10(-6) mol/l)-stimulated PGI2 synthesis was inhibited by verapamil (ID50 = 6 X 10(-5)) and calcium-free incubation media. It is concluded that in the rat penis PGI2 synthesis is principally under muscarinic control and is calcium transport-dependent. Since PGI2 is a vasodilator, these findings may be relevant to the increased blood flow into the penis associated with penile erection. They may also be relevant to the protection of the penile vasculature from thrombosis, since PGI2 is also a potent inhibitor of platelet aggregation.

Animals↗
PubMed1986

Epithelium removal increases the reactivity of human isolated tracheal muscle to methacholine and reduces the effect of verapamil.

Removal of the epithelium increased the sensitivity of human isolated tracheal smooth muscle to methacholine, producing a greater than 2-fold leftward shift in the concentration-response curve. Concomitantly, the ability of verpamil to lower the maximum contractile response was reduced in tissues without an intact epithelium. These findings suggest a role for the epithelium in modulating the reactivity of human and extend the findings of similar studies in experimental animals.

Adult↗
PubMed1986

Somatostatin's ability to inhibit gastric acid is not prostaglandin-mediated in the dog.

The role of prostaglandins in the effect of somatostatin to inhibit cholinergically stimulated gastric acid output was examined in gastric fistula dogs. Methacholine stimulation of gastric acid output to a maximum of 810 +/- 423 mu eq of [H+] per 15 min was inhibited by 10 nM somatostatin to the same extent either in the presence and/or the absence of indomethacin. In contrast, histamine-induced acid secretion was stimulated weakly by 10 nM somatostatin. Our data do not support a role for prostaglandins in somatostatin's action to inhibit cholinergically stimulated acid secretion.

Animals↗
PubMed1987

Paraoxon-induced decrease in the muscarinic acetylcholine receptor content in rat heart.

The regulation of the rat heart muscarinic acetylcholine receptor by injection of paraoxon (an acetylcholinesterase inhibitor) was characterized. No changes in receptor density in the four cardiac chambers were seen after two days. After three daily injections, however, significant decreases (20-25%) were observed in both atria and ventricles. These changes were associated with a 50% decrease in cardiac acetylcholinesterase activity. We were unable to demonstrate a change in the proportion or value of the apparent KDs for the two previously described affinity states of the receptor for the agonist methacholine. We found that the proportion of the high affinity form of the receptor was greater in atria than in ventricle (70 vs. 55%). Moreover, we also found that acetylcholinesterase activity was greater in the atria than ventricle. Although methacholine will produce down regulation of the muscarinic receptor in the perfused rat heart in 2.5 h (Reinhardt and Roskoski, 1983; J. Pharmacol. Exp. Ther. 226, 135), injection of large doses of methacholine failed to produce any receptor decreases within 6 h in vivo.

Acetylcholinesterase↗
PubMed1987

Regional differences in reactivity and in the influence of the epithelium on canine intrapulmonary bronchial smooth muscle responsiveness.

Differences in the reactivity and in the influence of the epithelium on responsiveness of canine 2nd and 3rd generation airway smooth muscle were examined. Epithelium-containing 3rd generation airways produced a greater maximum contraction and were more sensitive to methacholine and histamine, but not to KCl, than corresponding 2nd generation airways. Mechanical removal of the epithelium increased the sensitivity to methacholine and histamine in 2nd generation airways; there was also an increase in the maximum response elicited by histamine, but not by methacholine, in epithelium-free preparations. In contrast, there was no significant difference in the sensitivity to or the maximum response elicited by histamine or methacholine in epithelium-containing and epithelium-free 3rd generation airways. Epithelium removal had no effect on KCl-induced responses in either airway region. The inhibitory effects of verapamil (1 microM) against KCl- and methacholine-induced responses were identical in preparations containing and lacking the epithelium. The results support the postulate of an epithelium-derived inhibitory factor modulating airway smooth muscle reactivity. Furthermore, the influence of the epithelium exhibits regional differences, being greater in larger airways.

Animals↗
PubMed1987

The influence of omeprazole on the protective effects of secretagogues against ethanol-induced gastric ulceration in rats.

The influence of omeprazole on the antiulcer effects of histamine, methacholine and pentagastrin on ethanol-induced gastric ulceration was studied. Histamine 5 mg/kg, methacholine 500 micrograms/kg or pentagastrin 100 micrograms/kg pretreatment s.c. markedly reduced ethanol (50%, 10 ml/kg p.o.)-induced gastric ulceration in pylorus-ligated conscious rats, but significantly elevated the gastric secretory volume and acid output. Omeprazole pretreatment 50 mg/kg s.c. reduced gastric secretion and abolished the ulcer-protecting effects of the three secretagogues. The same doses of histamine, methacholine or pentagastrin did not significantly alter the gastric secretory volume but increased the total acid output of ex-vivo stomach chamber preparations in anaesthetised animals. Histamine worsened ethanol-evoked ulceration whereas methacholine and pentagastrin had no effect on the lesions. Omeprazole pretreatment did not prevent ulcer aggravation by histamine. It is concluded that the antiulcer effects of the three secretagogues in conscious animals are probably due to the increased secretory volume which lessens the ulcerogenic action of ethanol by its dilution. Omeprazole reduces the secretory volume and thus prevents the antiulcer effect of these secretagogues. The findings with histamine and omeprazole in the ex-vivo stomach experiments support the suggestion that it is unlikely that increased gastric acid secretion affects the ulcerogenicity of ethanol in rat stomach.

Animals↗
PubMed1988

Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists.

The relationship between bovine tracheal muscle contraction and phosphoinositide metabolism was studied with the muscarinic agonists, methacholine, oxotremorine, and McN-A-343. Analysis of the dose-response curves for contraction and inositol phosphates accumulation with these agonists demonstrated a direct relationship between the two parameters, with a considerable reserve of inositol phosphate production for the full contractile agonists, methacholine and oxotremorine, and no reserve for the partial agonist, McN-A-343.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1989

Muscarinic receptors in human airway smooth muscle are coupled to phosphoinositide metabolism.

In the present study we investigated whether muscarinic receptors in human airway smooth muscle are coupled to phosphoinositide metabolism as a possible transduction mechanism of contraction. Using isolated bronchial smooth muscle preparations, we found that the muscarinic agonist methacholine caused a time- and concentration-dependent accumulation of inositol phosphates in the presence of lithium, an effect which could be inhibited by atropine. Apart from its physiological significance, this finding may have great relevance for the biochemical investigation of cholinergic hyperresponsiveness in the airways of asthmatic patients.

Atropine↗
PubMed1989

Acetylcholine is an indirect inhibitory transmitter in the canine ileocolonic junction.

The effects of cholinergic agents, electrical stimulation and vasoactive intestinal polypeptide (VIP) were studied on transverse muscle strips of the canine ileum, ileocolonic junction and colon. Acetylcholine, methacholine and carbachol caused concentration-dependent contractions in the three gut tissues. Only acetylcholine (greater than 10(-5) M) evoked transient relaxations in the ileum and the ileocolonic junction before the onset of contractions. During contractions by noradrenaline, acetylcholine induced relaxations, which were enhanced by atropine; electrical stimulation also caused frequency-dependent relaxations. Propranolol or naloxone did not affect the relaxations. Hexamethonium, cocaine or lidocaine inhibited the relaxations induced by acetylcholine but not those evoked by electrical stimuli. Tetrodotoxin inhibited all relaxations, VIP did not evoke relaxation in the ileocolonic junction. These data indicate that acetylcholine stimulates nicotinic receptors on non-adrenergic non-cholinergic neurons, which do not release VIP or opioids. It is thus suggested that there is a nicotinic inhibitory innervation at the canine ileum and ileocolonic junction.

Acetylcholine↗
PubMed1990

Capsaicin selectively reduces airway responses to histamine, substance P and vagal stimulation.

Airway responsiveness to histamine, substance P, methacholine and bilateral electrical vagal stimulation was assessed in capsaicin-treated and control guinea pigs. In animals treated with capsaicin (50 mg/kg s.c.) 7 days before experiments, airway responsiveness to histamine, substance P and vagal stimulation was significantly reduced but responsiveness to methacholine was unchanged. The findings suggest that histamine and substance P, but not methacholine, require capsaicin-sensitive sensory afferent nerves for part of their actions.

Animals↗
PubMed1990

Effects of the dopamine receptor agonists, fenoldopam and quinpirole, in the rat stomach.

The effects of the DA1-receptor agonist, fenoldopam, and the DA2-receptor agonist, quinpirole, were studied with the longitudinal muscle of rat gastric fundus and circular muscle of rat gastric corpus, as there are contrasting reports about the receptors involved in the inhibitory effect of dopamine in these tissues. Quinpirole had no effect on basal tone in the longitudinal muscle of the rat gastric fundus and did not inhibit the sustained contractions induced by electrical field stimulation or by methacholine. Fenoldopam had no effect on the tone increased by methacholine but slightly potentiated the electrically induced contraction at the highest concentrations; it concentration dependently (10(-7)-3 X 10(-5) M) increased the basal tone. The contractile effect of fenoldopam was clearly antagonized by rauwolscine 10(-6) M, yohimbine 10(-6) M and phentolamine 3 X 10(-6) M plus propranolol 10(-5) M. The 5-HT receptor antagonist, methysergide, antagonized the fenoldopam-induced contractions in a non-competitive way. Fenoldopam and quinpirole had no effect on contractions induced in the circular muscle of the rat gastric corpus by methacholine or electrical field stimulation. They induced some contraction at basal tone, at their highest concentrations. As fenoldopam and quinpirole did not mimic the inhibitory effect observed with dopamine in the same models, no evidence was found for the presence of inhibitory dopamine receptors in rat gastric muscle. The contractile effect of fenoldopam in the longitudinal muscle of the fundus is probably due to an interaction with 5-HT receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Epithelium-derived inhibitory factor in human bronchus.

The potencies of histamine and methacholine were significantly increased by approximately 2- and 5-fold respectively in human non-diseased isolated bronchi on removal of the epithelium. In contrast, no increases in spasmogen potency were observed following epithelium removal in bronchi obtained from a sample of asthmatic human lung. The failure of epithelium removal to increase asthmatic bronchial sensitivity to histamine may have been due to a reduction in the release of an epithelium-derived inhibitory factor (EpDIF) resulting from disease-induced epithelial damage. A co-axial bioassay system in which endothelium-denuded rat aorta was used as the assay tissue was used to detect the release of a vasorelaxant EpDIF from human bronchial tissue. Histamine (100 microM) and methacholine (25 microM), in the presence of indomethacin (5 microM), reduced phenylephrine-induced tone in endothelium-denuded rat aorta in co-axial assemblies by 75 +/- 11 and 67 +/- 9% respectively. Removal of the bronchial epithelium abolished these responses, indicating that they were mediated by an EpDIF. It is possible that human airway smooth muscle is sensitive to this vasorelaxant EpDIF and that the absence of the source of this factor following epithelium removal caused the increases in sensitivity to spasmogens. Alternatively, the human bronchial epithelium may also release an EpDIF selective for airway smooth muscle.

Animals↗
PubMed1990

p-Fluoro-hexahydro-sila-difenidol: affinity for vascular muscarinic receptors.

The M3-selective antagonist, p-fluorohexahydro-sila-difenidol was used to characterize muscarinic receptors in two vascular preparations, the rabbit ear artery with an endothelium-dependent relaxation and the bovine coronary artery with an endothelium-independent contractile response. pKB values were consistent with the presence of M3 receptors, 7.9 and 7.5 in coronary and ear arteries, respectively. These findings confirm that muscarinic receptors of the rabbit ear artery and bovine coronary artery have similar characteristics and belong to the M3 subtype.

Animals↗
PubMed1992

K+ channel activator inhibition of neurogenic goblet cell secretion in guinea pig trachea.

A potassium (K+) channel activator, BRL 38227, inhibited goblet cell secretion in guinea-pig trachea induced by either electrical stimulation of the vagus nerves or acute inhalation of cigarette smoke, two stimuli which activate both cholinergic nerves and capsaicin-sensitive sensory nerves. BRL 38227 failed to inhibit methacholine- or substance P-induced goblet cell secretion which suggests that K+ channel activators inhibit neurogenic goblet cell secretion via a prejunctional effect on cholinergic and sensory nerves.

Animals↗