Inhibition Of Spontaneous Contractile Activity Research Articles

Adrenoceptor Function and Expression in Bladder Urothelium and Lamina Propria

To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria). The responses of isolated strips of porcine urothelium/lamina propria to noradrenaline, phenylephrine, and isoprenaline were obtained in the absence and presence of receptor subtype-selective antagonists. Quantitative reverse-transcriptase polymerase chain reaction was undertaken to assess the expression of adrenoceptor genes. The tissues expressed all α1- and β-adrenoceptor subtypes, with the α1A-, α1B-, and β2-adrenoceptors the predominant receptors at the messenger RNA level. In the functional experiments, the rate of phasic contractions and the basal tension were increased by the α1-adrenoceptor agonists phenylephrine (100 μM) and A61603 (10 μM). The rate and tension responses to phenylephrine were reduced by low concentrations of tamsulosin (3 nM) and RS100329 (10 nM) but were unaffected by BMY7378 (100 nM), prazosin (10 nM), and RS17053 (1 μM). In contrast, isoprenaline and salbutamol (both 1 μM) induced a relaxation of tissues and slowing of phasic contractions. The rate and tension responses to isoprenaline were inhibited by propranolol (100 nM) or a combination of CGP20712A (30 nM) and ICI118551 (70 nM). The rate responses were also significantly inhibited by ICI118551 alone (70 nM). Although all α1- and β-adrenoceptor subtypes were expressed in the pig urothelium/lamina propria, the α1A/L-adrenoceptor appeared to mediate increases in the contractile rate and tension. The β-adrenoceptor induced inhibition of spontaneous contractile activity appears to be predominately mediated by β2-adrenoceptors, with β1- and β2-adrenoceptors possibly involved in the tension responses.

Proteinase activated receptor‐2 (PAR‐2) inhibits spontaneous activity in rat colon via adrenergic nerves

Rat colonic smooth muscle shows spontaneous contractile activity which is generated by pacemaker cells. We have investigated whether this spontaneous activity can be modulated by proteinase activated receptor-2 (PAR-2), a G-protein coupled receptor activated by proteolytic cleavage. Strips of rat colon longitudinal muscle were suspended in organ baths and increasing concentrations of the PAR-2 mimetic peptide f-LIGRL were applied. f-LIGRL induced concentration-dependent inhibition of spontaneous contractile activity of rat colon that was sensitive to apamin, an inhibitor of small conductance Ca2+-activated potassium channels. Tetrodotoxin, an inhibitor of neurotransmission, blocked the effects of f-LIGRL as did phentolamine, an α-adrenoceptor antagonist. Propanolol, a β-adrenoceptor antagonist, had only small inhibitory effect on f-LIGRL-evoked responses. The adrenergic neuronal blocker guanethidine reduced responses to f-LIGRL supporting our conclusion that PAR-2 activation inhibits spontaneous contractile activity in the rat colon by releasing noradrenaline from adrenergic neurons to act on α-adrenoceptors on pacemaker cells. Supported by NSERC

Activation of proteinase activated receptor‐2 (PAR‐2) inhibits spontaneous activity in rat colon

Proteolytic cleavage of proteinase activated receptor‐2 (PAR‐2) reveals a tethered ligand which binds to and activates the receptor. Rat colonic smooth muscle shows spontaneous contractile activity which is generated by pacemaker cells. This study investigated the effects of PAR‐2 activation on spontaneous contractile activity in the isolated rat colon.Strips of rat colon longitudinal muscle were suspended in organ baths and increasing concentrations of trypsin, or the mimetic peptide FLIGRL, were applied. In some experiments carbachol was used to increase smooth muscle tone.Trypsin and FLIGRL each induced concentration‐dependent inhibition of spontaneous contractile activity of rat colon. Trypsin‐evoked relaxations (66.6±3.3; n=8) were abolished by apamin, an inhibitor of small conductance Ca2+‐activated potassium channels (SKCa). Similar results were obtained with FLIGRL (n=5). Cyclopiazonic acid, an inhibitor of sarcoplasmic reticulum Ca2+‐ATPase, also abolished the effects of trypsin (n=7). Neither trypsin (n=4) nor FLIGRL (n=4) reduced carbachol‐induced tone.In conclusion, activation of PAR‐2 inhibits spontaneous contractile activity in the rat colon via release of Ca2+ from intracellular stores and activation of SKCa channels. PAR‐2 activation is limited to pacemaker cells since no effect was observed on carbachol stimulated smooth muscle.Supported by NSERC

Inhibition by nitric oxide and nonadrenergic, noncholinergic (NANC) nerves is preserved in a canine model of extrinsic denervation: Implications for small bowel transplantation

Small bowel transplantation (SBT) is complicated by changes in graft motility, especially in the early postoperative period. This dysmotility may be related in part to the extrinsic denervation necessitated by the procedure, but specific neurotransmitter response to SBT is incompletely understood. The aim of this study was to evaluate the role of nitric oxide and nonadrenergic, noncholinergic (NANC) enteric neural input in the nonimmunologic etiology of the dysmotility seen after SBT. A technique of jejunoileal extrinsic denervation (without disruption of mesenteric vascular supply) was used as a model of canine jejunoileal autotransplantation to avoid potential confounding factors such as ischemia-reperfusion and postallotransplant immunologic effects. Longitudinal smooth muscle strips from ileum and jejunum were studied with in vitro tissue chamber methodology at 0, 2, and 8 weeks after this experimental model to explore early and late effects of denervation. Effects of exogenous nitric oxide (NO) and electric field stimulation (EFS), which releases native, endogenous enteric neurotransmitters) were evaluated in neurally intact control dogs and those undergoing extrinsic denervation. Exogenous NO caused a dose-dependent inhibition of spontaneous contractile activity and in some muscle strips a decrease in basal tone in both groups of dogs. These effects were unchanged by neural blockade with tetrodotoxin and preserved after extrinsic denervation. EFS produced inhibition of spontaneous contractile activity in ileum and a complex, inconsistent response in jejunum. The response to EFS in both ileum and jejunum was unchanged after extrinsic denervation. Nitric oxide inhibits contractile activity in canine longitudinal muscle of small bowel. Motility changes seen after this large animal model of extrinsic denervation are not caused by changes in NO or NANC neural function. The variability observed between different segments of intestine is important to consider in the context of SBT.

Androgens Induce Relaxation of Contractile Activity in Pregnant Human Myometrium at Term: A Nongenomic Action on L-Type Calcium Channels1

It has long been accepted that progesterone regulates uterine contractile activity. However, little is known about the role of androgens in female physiology, and their importance and biological function on myometrial contractility so far have received limited attention. In this work, we examined the direct effect of androgens on the contractile activity of the isolated human myometrium. Myometrial biopsies were obtained, with consent, from pregnant women undergoing elective cesarean section at term. Each androgen tested (dehydroepiandrosterone, testosterone, 5alpha- and 5beta-dihydrotestosterone, androsterone, or androstanediol) caused a concentration-dependent inhibition of spontaneous contractile activity; a relaxing effect of these androgens was also observed on the contractions induced by high potassium (KCl) solution. Interestingly, nonpregnant myometrium was also sensitive to androgen-induced relaxation. 5beta-Dihydrotestosterone (5beta-DHT) was dramatically more potent than the other androgens in inducing myometrial relaxation in all preparations. Relaxation response to androgens had very rapid time courses and was affected by neither the specific antiandrogen (flutamide) nor inhibitors of protein synthesis (cycloheximide) and transcription (actinomycin D), implying that androgens act through a nongenomic mechanism. Importantly, 5beta-DHT significantly reduced the increase in intracellular calcium concentration associated with exposure to KCl in human myometrial smooth-muscle cells loaded with Fura-2-AM. The blockade of l-type calcium channels seems to be involved in the nongenomic relaxing action of androgens. These observations demonstrate that androgens may play a crucial role in maintaining pregnancy.

Nitric oxide donor-induced inhibition of pregnant rat uterine spontaneous contractile activity and release of nitric oxide from uterus measured by microdialysis

Our aim was to study whether nitric oxide (NO) donor-induced inhibition of pregnant rat myometrium contractility correlates with the release of NO. Uterine rings from mid-pregnant and late pregnant Sprague-Dawley rats were used for isometric tension recording. Concentration-response relationships to sodium nitroprusside (SNP), nitroglycerine (NTG) and diethylamine (DEA)/NO were assessed. The time course of NO release after addition to the organ chambers of the 3 NO-donors was assessed by the detection of NO products NOx (NO3+NO2) using the microdialysis probe by a HPLC-NO detector system. DEA/ NO induced greater inhibition of the spontaneous contractile activity of uterine rings from mid-pregnant rats than SNP or NTG. In uterine rings from late pregnant rats, however, the maximal inhibition of the contractility by all 3 NO-donors were significantly less. The NOx levels measured in the uterine ring walls from either mid-pregnant or late pregnant rats significantly increased after DEA/ NO as compared to the basal levels or the levels after NTG or SNP. The decrease of NO-donor-induced inhibition of rat myometrium contractility, with unchanged formation of NOx, at term, suggests that the changes in NO signaling are responsible for gestational age-dependent attenuation of the inhibitory effect.

Roles of potassium channels and nitric oxide in modulation of uterine contractions in rat pregnancy

Objective: We sought to study the involvement of potassium channels in the inhibition by nitric oxide of spontaneous contractions in isolated uterine rings from midterm and term pregnant rats. Study Design: Uterine rings from Sprague-Dawley rats at midterm and term gestation were used for isometric tension recording. The inhibition of spontaneous contractile activity by potassium channel openers and nitric oxide was studied in the absence and presence of potassium channel inhibitors. Results: The adenosine triphosphate–dependent potassium channel opener levcromakalim inhibited spontaneous contractions in rings from both midterm and term pregnant rats in a concentration-dependent manner, and the effects were significantly attenuated by pretreatment with selective inhibitor of the adenosine triphosphate–dependent potassium channel inhibitor glibenclamide. The opener of calcium-dependent potassium channel NS 1619 inhibited spontaneous contractions in rings from midterm but significantly less so in rings from term pregnant rats in a concentration-dependent manner, and the effect was significantly attenuated by pretreatment with potassium channel inhibitors tetraethylammonium and tetrabutylammonium but not with glibenclamide. Rings from midterm and term pregnant rats were more sensitive to the inhibitory effect of levcromakalim compared with NS 1619. Nitric oxide donor diethylamine–nitric oxide inhibited spontaneous contractions in rings from midterm but significantly less in rings from term pregnant rats in a concentration-dependent manner, and the effect was attenuated by tetraethylammonium and tetrabutylammonium but not by glibenclamide. Conclusions: There is gestational age–dependent refractoriness to calcium-dependent potassium but not adenosine triphosphate–dependent potassium channel opener–induced inhibition of spontaneous contractile activity of isolated rat uterine rings. Nitric oxide inhibits uterine contractions by opening of calcium-dependent potassium channels in pregnant rat myometrium. Refractoriness to nitric oxide toward term may result from decreased probability to open or number of calcium-dependent potassium channels. (Am J Obstet Gynecol 1999;181:649-55.)

Involvement of K+ATPChannels in Nitric Oxide-Induced Inhibition of Spontaneous Contractile Activity of the Nonpregnant Human Myometrium

Nitric oxide (NO), an important endogenous substance, is known to be a strong relaxant of smooth muscle, including myometrium. It has been postulated that the relaxing effect of NO on smooth muscle is achieved by the stimulation of soluble guanylyl cyclase, which leads to an increase in the cyclic guanosine 3′,5′-monophosphate (cGMP) levels and hyperpolarization of the cellular membrane. The aim of our study was to investigate the involvement of K+ATPchannels in the mechanism of cGMP-independent nitric oxide-induced inhibition of contractile activity of the nonpregnant human myometrium, obtained at hysterectomy. Nitric oxide's influence on contractile activity was recorded in the presence of methylene blue and glybenclamide, blockers of soluble guanylyl cyclase and K+ATPchannels, respectively. Nitric oxide, generated by the NO donor DEA/NO, caused a dose-dependent inhibition of the spontaneous contractile activity of human nonpregnant myometrium. Preincubation with methylene blue (5 μM) did not prevent NO-induced relaxation of uterine strips, while 1.5 μM glybenclamide blocked this effect. Our results indicate that nitric oxide relaxes human non-pregnant uterus through K+ATPchannels, independent of the cGMP pathway.

Nitric oxide mediated inhibition of contractile activity in the human uterine cervix.

Nitric oxide (NO) is an important modulator of contractile activity in various tissues. The aim of the present study was to investigate the possible existence of an NO system within the human uterine cervix and to study the effects of NO on the cervix in early pregnancy. Cervical tissue specimens were obtained from 24 women in connection with first trimester legal abortion. NADPH diaphorase staining was used to identify nitric oxide synthase activity within the cervical tissue. Cylindrical tissue specimens were mounted in organ bath chambers for isometric registration of contractile activity. The presence of a functional NO system in the cervix was investigated by adding either sodium nitroprusside or spermine NONOate, two different NO donors, or 8-bromo cGMP, an analogue of the second messenger cyclic guanosine monophosphate (cGMP), to the organ baths. Positive NADPH diaphorase staining was clearly observed in the walls of blood vessels, in cervical smooth muscle cells, and cells scattered in the connective tissue. The NO donating drugs sodium nitroprusside and spermine NONOate both caused a dose-dependent inhibition of spontaneous contractile activity with significant inhibition at concentrations of 10(-5) and 10(-7) M respectively. Furthermore, the participation of NO in the regulation of cervical contractility was indicated by a significant concentration-dependent inhibition of spontaneous contractions when 8-bromo cGMP (10(-5)-10(-3) M) was added to the organ baths. The study indicates the existence of an NO system within the human uterine cervix and a role of NO in control of cervical function.

P.1.086 Analgesic, sedative and antidepressant effects of noradrenergic antidepressants related to beta-adrenoceptors

To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria).The responses of isolated strips of porcine urothelium/lamina propria to noradrenaline, phenylephrine, and isoprenaline were obtained in the absence and presence of receptor subtype-selective antagonists. Quantitative reverse-transcriptase polymerase chain reaction was undertaken to assess the expression of adrenoceptor genes.The tissues expressed all α1- and β-adrenoceptor subtypes, with the α1A-, α1B-, and β2-adrenoceptors the predominant receptors at the messenger RNA level. In the functional experiments, the rate of phasic contractions and the basal tension were increased by the α1-adrenoceptor agonists phenylephrine (100 μM) and A61603 (10 μM). The rate and tension responses to phenylephrine were reduced by low concentrations of tamsulosin (3 nM) and RS100329 (10 nM) but were unaffected by BMY7378 (100 nM), prazosin (10 nM), and RS17053 (1 μM). In contrast, isoprenaline and salbutamol (both 1 μM) induced a relaxation of tissues and slowing of phasic contractions. The rate and tension responses to isoprenaline were inhibited by propranolol (100 nM) or a combination of CGP20712A (30 nM) and ICI118551 (70 nM). The rate responses were also significantly inhibited by ICI118551 alone (70 nM).Although all α1- and β-adrenoceptor subtypes were expressed in the pig urothelium/lamina propria, the α1A/L-adrenoceptor appeared to mediate increases in the contractile rate and tension. The β-adrenoceptor induced inhibition of spontaneous contractile activity appears to be predominately mediated by β2-adrenoceptors, with β1- and β2-adrenoceptors possibly involved in the tension responses.

Pinaverium acts as L-type calcium channel blocker on smooth muscle of colon.

The effect of pinaverium was electrophysiologically characterized and compared with the established L-type calcium channel blockers diltiazem, D600, and nitrendipine on canine colonic circular smooth muscle. Effects were studied on the electrical activity of the smooth muscle cells, in particular the spontaneously occurring slow wave. In addition, effects were examined on spontaneous contraction patterns and contractile activities generated by stimulation of cholinergic nerves or directly by stimulating muscarinic receptors. Effects were also examined on excitation of NO-releasing intrinsic nerves. Pinaverium bromide affected the slow wave by selectively inhibiting the plateau potential that is associated with generation of contractile activity. Pinaverium, similar to diltiazem and D600, produced reductions in cholinergic responses as well as spontaneous contractions. The IC50 values for inhibition of cholinergic responses for pinaverium, diltiazem, and D600 were 1.0 x 10(-6), 4.1 x 10(-7), and 5.3 x 10(-7) M, respectively. The IC50 values for inhibition of spontaneous contractile activity for pinaverium, diltiazem, and D600 were 3.8 x 10(-6), 9.7 x 10(-7), and 8.0 x 10(-7) M, respectively. Increases in contractility by carbachol were abolished by pretreatment with either pinaverium or D600. In addition, neither pinaverium nor D600 had any effects on the inhibitory NO-mediated relaxations. These data provide a rationale for the use of pinaverium in the treatment of colonic motor disorders where excessive contraction has to be suppressed.

Apamin‐sensitive and ‐insensitive components of inhibitory junction potentials in rat caecum: role of nitric oxide

1. The non-adrenergic non-cholinergic (NANC) inhibitory response to electrical field stimulation (EFS) in circular muscle from rat caecum was investigated using the single sucrose-gap technique. EFS with single pulses evoked hyperpolarization oral inhibitory function potential (IJP) of the membrane associated with muscular relaxation or with transient inhibition of spontaneous contractile activity. 2. The amplitude and the duration of the IJPs were enhanced by using train stimulation at increasing frequency. 3. Apamin (10(-7) M) reduced the amplitude of IJPs at all frequencies tested. 4. N omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M, 5 x 10(-4) M), but not D-NAME, caused a concentration dependent decrease in the amplitude of IJPs at all frequencies tested. L-Arginine (10(-3) M) prevented these effects. 5. L-NAME (5 x 10(-4) M) caused the disappearance of the apamin-resistant IJP-component, evoked by single pulse or by low frequency trains. 6. Sodium nitroprusside (SNP) (10(-4) M), a nitric oxide (NO) donor, induced hyperpolarization of membrane potential and muscular relaxation. SNP-induced effects were not affected by pretreatment of the muscle strips with effective concentrations of tetrodotoxin, apamin, and L-NAME. 7. P2-purinergic antagonists, reactive blue 2 (up to 5 x 10(-4) M) and suramin (up to 3 x 10(-4) M), failed to affect the evoked IJPs. 8. These results show that, in rat caecum, the NANC response to electrical stimulation is composed of two distinguishable components: an apamin-resistant and an apamin-sensitive component. NO or a related compound is mainly involved in the mediation of the apamin-resistant component, while ATP is not the mediator responsible for the apamin-sensitive component.

Innervation of the foregut of the cockroach Leucophaea maderae and inhibition of spontaneous contractile activity by callatostatin neuropeptides

Abstract. The innervation of the gut of the cockroach Leucophaea madera (F.) has been studied by means of wholemount immunocytochemistry with antisera raised against Leu‐callatostatin, a cockroach allatostatin homologue identified from neuropeptide isolation and gene studies in the blowfly Calliphora vomitoria. Leu‐callatostatin‐imunoreactive neurones in the brain, with axon trajectories in the stomatogastric nervous system, innervate the foregut and midgut. Neurones in the last abdominal ganglion supply the hindgut and the midgut via the proctodeal nerve. In addition to a rich callatostatin‐immunoreactive nerve supply, the midgut, including the midgut caeca, contain numerous callatostatin‐immunoreactive endocrine cells. Physiological studies show that the spontaneous contractile activities of the foregut, but not the hindgut, are inhibited by callatostatin neuropeptides. Leu‐callatostatin 3 was the most potent of the range of Leu‐and Met‐callatostatins tested, with a dose‐dependent response between 10‐13 and 10‐7 M. This is similar to the results obtained with the previously identified myoinhibitory peptide of L. maderae, leucomyosuppressin. However, this peptide, with a different type of structure to the allatostatins, inhibits both foregut and hindgut motility equally. Experiments with a series of analogues of the Met‐callatostatins showed that the free acid (as opposed to the carboxyamidated peptide) and N‐terminally truncated peptides were inactive. These morphological and physiological results are thought to be representative of the, as yet unidentified, naturally occurring allatostatin homologues of L. maderae. This family of peptides should be added to the increasing list of insect gut myoinhibitory substances.

Contractile activity modulates myosin heavy chain-beta expression in neonatal rat heart cells

To determine whether spontaneous contractile activity affected the expression of myosin heavy chain isoenzymes in cultured neonatal rat heart cells, ventricular myocytes were isolated from 2-day-old rat pups by collagenase digestion and cultured for 24-96 h in the presence and absence of verapamil (10 microM), KCl (50 mM), or dihydropyridine receptor antagonists that produced contractile arrest. Inhibition of spontaneous contractile activity was associated with significant reductions in total myosin heavy chain (MHC) content and synthetic rates. Electrophoretic analysis of MHC isoenzymes indicated that MHC-beta protein rapidly disappeared from arrested cells, whereas MHC-alpha isoenzyme levels were less affected. In association with these protein changes, mRNA transcript levels for MHC-beta were markedly reduced in quiescent cells, whereas mRNA transcript levels for several other contractile protein genes were relatively less affected. Inhibition of contractile activity and MHC-beta expression were reversible upon removal of the arresting agents. Furthermore, the decrease in MHC-beta mRNA levels in arrested myocytes could be prevented by direct activation of protein kinase C with phorbol 12-myristate 13-acetate (without restoration of contractile activity). Conversely, MHC-beta mRNA levels in beating cells were reduced by treatment with staurosporine (a selective protein kinase C inhibitor). Thus contractile arrest (produced by either L-channel blockade or membrane depolarization) inhibited the accumulation of MHC-beta in cultured neonatal rat heart cells via a pretranslational mechanism. These effects may occur in response to the modulation of signaling system(s) involving mechanical "stretch" transduced via protein kinase C.

Direct actions of catecholamines on subsections of the canine colon wall

DIRECT ACTIONS OF CATECHOLAMINES ON SUBSECTIONS OF THE CANINE COLON WALL. K.D. Keef, B.W. Frey and T.K. Smith. Department of Physiology, University of Nevada, Reno, NV, 89557. The purpose of the present study was to characterize the effects of epinephrine (Epi) and norepinephrine (NE) on the contractile activity of colonic smooth muscle. The wall of the colon is functionally complex (e.g., Smith et al, 1987) thus the actions of catecholamines were tested on subsections which contained only one muscle type and one pacemaking/plexus region. These segments included: 1) Longitudinal muscle (LM), 2) Myentenk circular muscle (MCM) and 3) Submucosal circular muscle (SCM). Segments of LM and MCM contained the myenteric plexus region whereas SCM contained the submucosal plexus region. Responses in these segments were compared to: 4) Whole circular muscle (WCM) which included the entire circular muscle layer and both plexus regions. All experiments were carried out in the presence of 5x16’M tetrodotoxin. Epi addition (10~7-10~sM) led to inhibition of spontaneous contractile activity in LM and MCM. In SCM and WCM Epi produced an initial excitation which declined with time and was followed by inhibition. Excitation never exceeded 10% of the maximum response elicited with ACh (1tiM). Addition of Epi to tissues rhythmically contracting with ACh (5xlw’M) led to inhibition in all segments. Similar results were obtained for NE. Inhibition was found to be due to both alpha and beta receptor stimulation whereas excitation was due specifically to alpha receptor stimulation. The results indicate that the actions of catecholamines on WCM are largely a consequence of the events which occur in the s;lbmucosal pacemaking region. These actions include weak alpha receptor mediated excitation and strong inhibition induced by both alpha and beta adrenergic receptors. Grant support DK 41315.

Sympathetic control of motility, fluid transport, and transmural potential difference in the rabbit ileum

Both intestinal motility and intestinal fluid and electrolyte transport are influenced by the sympathetic nervous system. The aim of this study is to examine the relationship between the sympathetically induced inhibition of spontaneous contractile activity and epithelial function, monitoring simultaneously motility, fluid transport, and transmural potential difference (PD) in the rabbit ileum. Experiments were performed in vitro to eliminate any possible indirect effects on intestinal function caused by alterations in intestinal blood flow. Perivascular nerve stimulation induced an inhibition of spontaneous motility, a fall in transmural PD (toward more lumen positive), and an enhanced fluid absorption. The sympathetically induced inhibition of motility was abolished by the beta-adrenoceptor antagonist, propranolol, whereas the subsequent administration of phentolamine, the alpha-adrenoceptor antagonist, was required to abolish the fall in transmural PD. Thus the sympathetic nervous system is capable of simultaneously influencing intestinal motility and fluid and electrolyte function. However, separate but parallel neural mechanisms control the smooth muscle and epithelial responses; the inhibition of motility is beta-mediated, while alpha-receptors alter fluid and electrolyte transport.

Inhibition of spontaneous contractile activity in isolated human detrusor muscle strips by vasoactive intestinal polypeptide: R. B. Kinderand A.R. Mundy. Br J Urol 57:20–23, (February), 1985

Inhibition of spontaneous contractile activity in isolated human detrusor muscle strips by vasoactive intestinal polypeptide: R. B. Kinderand A.R. Mundy. Br J Urol 57:20–23, (February), 1985

Inhibition of spontaneous contractile activity in isolated human detrusor muscle strips by vasoactive intestinal polypeptide.

In a study of 75 isolated human detrusor muscle strips, spontaneous contractions and an associated sustained rise in basal tension were observed in 43 (57%). Vasoactive intestinal polypeptide (VIP) caused significant reductions in the frequency and amplitude of spontaneous contractions and a fall in basal tension. The results suggest that VIP may have a role as an inhibitor of spontaneous activity in the human detrusor.

The effect of prostaglandin I 2 on the contractility of the term pregnant human myometrium

Small myometrial strips were dissected from the upper and lower segments of the term pregnant human uterus. The specimens were superfused in organ chambers and contractile activity was recorded isometrically. In strips from the upper segment, prostacyclin (PGI 2), induced an initial excitatory response followed in the majority of experiments by transient inhibition. In the lower segment the response was generally the same although direct inhibition without initial stimulation occurred in some cases. During the period of inhibition the specimens were refractory to iterated exposure to PGI 2. Furthermore, during this period of PGI 2-induced inhibition the muscle strip was also refractory to PGE 2 but responded to PGF 2α and oxytocin by stimulation. After inhibition of spontaneous contractile activity induced by indomethacin PGI 2 induced an excitatory response. The results do not indicate any critical change in the myometrial responsiveness of the upper uterine segment to PGI 2 during labor. In strips from the lower segment obtained before labor there tended to be a dominance of non-responders and inhibition only as compared to the results during labor. Nevertheless, whether or not PGI 2 under physiological or pharmacological conditions has any significant influence on the contractility of the term pregnant human uterus, still remains obscure. As judged from earlier reports from our laboratory and the present study it is evident that the uterine vessels are considerably more sensitive to the action of PGI 2 than the myometrium.

Characterization of the β-adrenergic inhibition of motility in cat colon strips

The inhibition of spontaneous contractile activity in isolated cat colon strips by isoprenaline, prenalterol and terbutaline was studied. Isoprenaline produced a concentration-dependent complete inhibition with an EC 50 of 6.18 nM. Prenalterol and terbutaline produced a concentration-dependent partial inhibition of 68 and 75% respectively, with EC 50 of 0.52 and 0.43 μM respectively. The inhibitory effects of the three agonists were blocked by metoprolol and IPS 339 in such a way as to suggest that the prenalterol effect was mediated by β 1-adrenoceptors and the terbutaline effect was mediated by β 2-adrenoceptors, whereas the effect of isoprenaline appeared to be mediated by both types of receptors. Thus, the results indicate that both β 1- and β 2-adrenoceptors are involved in the adrenergic inhibition of spontaneous contractile activity in the cat colon strip. Qualitative effects of prenalterol and terbutaline on the spontaneous contractile activity in the cat colon strip indicated that the β 1-adrenoceptor-mediated effects may be related to inhibition of the activity in cholinergic neurons, whereas the β 2-adrenoceptors may be acting on the smooth muscle cells per se.