Effects of acetylcholine and nitroprusside on cGMP-dependent protein kinase in the perfused rat heart

The effects of acetylcholine and sodium nitroprusside on the activity of cGMP-dependent protein kinase were studied in the perfused rat heart. Acetylcholine produced a dose-dependent increase in cGMP levels and cGMP-dependent protein kinase activity, and reduced the force of contraction. Both acetylcholine and sodium nitroprusside produced rapid increases in cardiac cGMP, with nitroprusside being the more potent agent. Only acetylcholine, however, raised the activity ratio of the cGMP-dependent protein kinase and decreased the force of contraction. Whereas acetylcholine and nitroprusside were slightly additive in their effects on total cGMP levels, the increase in the activity ratio of the cGMP-dependent protein kinase and the decrease in the force of contraction produced by acetylcholine were unchanged by nitroprusside. The results suggest that the cGMP produced by acetylcholine, but not nitroprusside, was coupled to protein kinase activation in this tissue.     

Effects of neurotransmitters on the spontaneous activity of the mouse uterine in situ at various stages of pregnancy

Serotonin, acetylcholine and noradrenaline neither initiated nor indicated the uterus contractility in immature or pregnant mice; they, however, regulated the uterine motility in respect to the neurotransmitters concentration and the hormonal status of females. Inactivation of the beta-receptors in longitudinal muscle fibres prevented the drop in the myometric contraction force, whereas blockade of the alpha-receptors in circular muscle fibres prevented the reduction of the myometric tone induced by noradrenaline. The data obtained suggests that the circular muscle is responsible for the myometric tone while the longitudinal muscle is responsible for the uterus contraction force.     

Role of prostaglandins and leukotrienes in the synergistic effect of oxytocin and corticotropin-releasing hormone (CRH) on the contraction force in human gestational myometrium.

We have recently demonstrated that corticotropin releasing hormone (CRH) potentiates the contractile response to oxytocin of human gestational myometrium, using a high flow microsuperfusion system and electrical field stimulation. We now report this potentiation to be equivalent to that of 1 nM prostaglandin F2 alpha (PGF2 alpha), while 10 nM PGF2 alpha did not potentiate the response to oxytocin. Prostaglandin E2 (PGE2) also showed no augmentation of the contraction force of the myometrium in response to oxytocin. The CRH potentiated response was inhibited by the lipoxygenase and cyclooxygenase inhibitor BW755C (1 microM) and by indomethacin (0.1 microM), but not by the lipoxygenase inhibitor BW4C (1 microM). Measurements of prostaglandins in the superfusate showed no significant trends. It is concluded that the potentiation of contraction force to oxytocin by CRH is dependent on prostaglandins, probably PGF2 alpha and that leukotrienes, generated via the lipoxygenase pathway are not involved.     

Regulation of cardiac cyclic GMP-dependent protein kinase

An assay method based on the ability of high concentrations of Mg²⁺ to stimulate phosphorylation of histone in the presence of low concentrations of ATP was developed for the measurement of cyclic GMP-dependent protein kinase activity ratios (activity -cyclic GMP/activity + cyclic GMP). In tissues which contain only trace amounts of cyclic GMP-dependent protein kinase, the basal activity ratios were high due to interference from a cyclic nucleotide-independent protein kinase. In order to study the regulation of the cardica cyclic GMP-dependent protein kinase, factors affecting the equilibrium between the active and inactive forms of the enzyme were determined. Since the rate of dissociation of cyclic GMP from its binding site(s) was relatively slow at 0–4°C at pH 7.0, the amount of time required to process tissue samples was the major limiting factor for preserving the equilibrium between active and inactive forms of the enzyme. Dilution of heart tissue extracts at 0–4°C did not significantly alter the activity ratio of the enzyme under conditions of basal or elevated cyclic GMP levels. Experiments using charcoal or exogenous cyclic GMP-dependent protein kinase in the homogenizing medium demonstrated that the release of sequestered cyclic GMP was not responsible for the elevation of the cyclic GMP-dependent protein kinase activity ratios by agents like acetylcholine. Therefore, the assay reflected in part, at least, the retention of kinase-bound cyclic GMP in the tissue extracts. The effects of acetylcholine and sodium nitroprusside on cyclic GMP levels, the cyclic GMP-dependent protein kinase activity ratios, and force of contraction were studied in the perfused rat heart. Both agents produced rapid, dose-dependent increases in cardiac cyclic GMP. Optimal concentrations of acetylcholine produced a 2–3-fold increase in the levels of cyclic GMP and an increase in the cyclic GMP-dependent protein kinase activity ratio. No significant effect of acetylcholine on cyclic nucleotide-independent protein kinase activity was observed. Associated witth the acetylcholine-induced protein kinase, factors affecting the equilibrium between the active and inactive forms of the enzyme were determined. Since the rate of dissociation of cyclic GMP from its binding site(s) was relatively slow at 0–4°C at pH 7.0, the amount of time required to process tissue samples was the major limiting factor for preserving the equilibrium between active and inactive forms of the enzyme. Dilution of heart tissue extracts at 0–4°C did not significantly alter the activity ratio of the enzyme under conditions of basal elevated cyclic GMP levels. Experiments using charcoal or exogenous cyclic GMP-dependent protein kinase in the homogenizing medium demonstrated that the release of sequestered cyclic GMP was not responsible for the elevation of the cyclic GMP-dependent protein kinase activity ratios by agents like acetylcholine. Therefore, the assay reflected in part, at least, the retention of kinase-bound cyclic GMP in the tissue extracts. The effects of acetylcholine and sodium nitroprusside on cyclic GMP levels, the cyclic GMP-dependent protein kinase activity ratios, and force of contraction were studied in the perfused rat heart. Both agents produced rapid, dose-dependent increases in cardiac cyclic GMP. Optimal concentrations of acetylcholine produced a 2–3-fold increase in the levels of cyclic GMP and an increase in the cyclic GMP-dependent protein kinase activity ratio. No significant effect of acetylcholine on cyclic nucleotide-independent protein kinase activity was observed. Associated with the acetylcholine-induced increase in cyclic GMP and the cyclic GMP-dependent protein kinase activity ratio was a reduction in the force of contraction. In contrast, nitroprusside produced little or no increase in the cyclic GMP-dependent protein kinase activity ratio despite increasing the level of cyclic GMP 8–10-fold. Nitroprusside also had no effect on contractile force. In combination, nitroprusside and acetylcholine produced additive effects on cyclic GMP levels, but protein kinase activation and force of contraction were similar to those seen with acetylcholine alone. The results suggest that the cyclic GMP produced by acetylcholine in the rat heart is coupled to activation of the cyclic GMP-dependent protein kinase, while that produced by nitroprusside is not.     

Amiloride inhibits contraction and serotonin modulation of Aplysia muscle

1. Serotonin (5-HT) potentiates acetylcholine (ACh)-elicited contractions of Aplysia buccal muscles. Serotonin potentiation was significantly reduced by 0.03 mM, 0.1 mM, and 0.3 mM amiloride. 2. Unpotentiated ACh-elicited contractions were significantly reduced by 0.1 mM and 0.3 mM amiloride. 3. Amiloride reduced ACh-elicited depolarization. The reduction in contraction caused by 0.3 mM amiloride (to 16% of control) was larger than could be explained by the reduction in depolarization (86% of control). 4. Amiloride had no effect on tension in skinned muscle fibers, indicating that amiloride probably did not have a direct effect on contractile mechanisms. 5. Potentiation of contraction produced by zero sodium (Tris substituted, 0 Na-Tris) medium could be abolished by 0.3 mM amiloride. 6. Zero Na-Tris increased 45Ca influx 2.7-fold. In the presence of 0.3 mM amiloride, 0 Na-Tris increased 45Ca influx only 1.4-fold. 7. Amiloride (0.3 mM) reduced the elevation of muscle cAMP caused by 10(-6) M 5-HT by 60%. Zero Na-Tris did not cause a change in muscle cAMP.     

Bombesin potentiates the effect of acetylcholine on isolated strips of fish stomach.

The interaction between bombesin and acetylcholine acting on smooth muscle of the stomach wall was investigated in two species of teleost fish. Oncorhynchus mykiss (rainbow trout) and Gadus morhua (Atlantic cod). Acetylcholine or bombesin alone has an excitatory effect on the stomach muscle. The effect on contraction amplitude of acetylcholine (10(-6)-10(-5) M) alone is about 10-times greater than the effect of bombesin (10(-9)-10(-7) M). In molar terms however, bombesin is more potent than acetylcholine. Bombesin (10(-8)-10(-7) M) added 0.5-3 min prior to acetylcholine potentiates the effect of acetylcholine in a dose-dependent manner. The potentiation is most pronounced in circular muscle preparations, but is present also in longitudinal muscle preparations. Bombesin affects the response to carbachol (10(-6) M) with a similar potentiation, indicating that the potentiation is not caused by inhibition of choline esterase activity. Atropine (10(-6)-10(-5) M) abolishes the response to bombesin plus acetylcholine as well as the response to acetylcholine alone. Tetrodotoxin (10(-6) M) does not block the effect of acetylcholine, bombesin or the combination acetylcholine plus bombesin. Substance P (10(-9)-10(-7) M) which has a similar excitatory effect on the stomach muscle as bombesin, does not potentiate the effect of acetylcholine. Immunohistochemistry has shown the presence of strong bombesin-like immunoreactivity in stomach nerves of the cod and weak bombesin-like immunoreactivity in rainbow trout nerves. In addition, bombesin-like immunoreactivity was demonstrated in endocrine cells in the gastric and intestinal mucosa of both species. It is concluded that bombesin, contained either in nerve fibres or in mucosal endocrine cells, specifically potentiates the effect of acetylcholine in the fish stomach.     

Effects of hypoxia,simulated ischemia and reoxygenation on the contractile function of human atrial trabeculae

Hypoxia, ischemia and reoxygenation cause contractile dysfunction which will be characterized by the time course of isometric contraction of human atrial trabeculae. Post-rest potentiation (PRP) and postextrastimulatory potentiation (PEP) were elicited to obtain indirect information about the role of the sarcoplasmic reticulum (SR) in excitation-contraction coupling. As lipid peroxidation could cause SR dysfunction, thiobarbituric acid reactive substances (TBARS) were measured. After 30 min of hypoxia (H) or simulated ischemia (H combined with acidosis-SI), contractile force decreased to 15% and 6%, respectively, of control (p <- 0.05), whereas the normalized rate of both contraction and relaxation increased. In group H, rapid reoxygenation produced a recovery of contractile force to about 60%. After post-hypoxic reoxygenation the TBARS concentration was increased. In group SI, rapid reoxygenation and a rather gradual correction of acidosis produced complete recovery of contractile force. PRP and PEP were maintained during H and SI. Particularly post-ischemic reoxygenation caused a marked depression of PRP and partly of PEP. Thus, alteration of SR Ca²⁺ handling occurs predominantly during reoxygenation rather than during H or SI, probably associated with the damaging effect of increased oxygen radicals. The depression of potentiation occured along with delayed relaxation, temporary increased resting force, mechanical alternans, and spontaneous activity which are further characteristics for SR dysfunction. Thus, for a possibly beneficial effect of low pH during SI combined with its gradual correction during reoxygenation on the recovery of contractile function, developed force should not be the only index.     

Functional role of serotonergic neuromodulation in Aplysia.

The serotonergic metacerebral cell (MCC) of the mollusk Aplysia produces slow synaptic potentials in motor neurons of the buccal muscle, and increases the rate of ongoing rhythmic burst output of the buccal ganglion. In addition, the MCC acts peripherally to enhance the strength of buccal muscle contractions that are produced by firing of motor neurons. The potentiation of contraction is not associated with any detectable changes of resting membrane potential of muscle cells. Although MCC activity produces a small enhancement of excitatory junctional potentials, several experiments clearly indicate that the MCC has a direct potentiating effect on excitation-contraction coupling. The data suggest that potentiation of contraction might be mediated by cAMP. For example, activity of the MCC enchances the rate of accumulation of cAMP in buccal muscle, application of phosphodiesterase resistant analogs of cAMP potentiates muscle contraction, and a phosphodiesterase inhibitor enhances the effect of MCC stimulation. Recordings from free-moving animals indicate that the MCC becomes activated by exposure of the animal to food stimuli, and that the activation parallels the presence of a food-arousal state. Food-arousal is characterized by enhanced strength and increased frequency of biting responses. Both these effects can result from activity of the MCC. Thus, in this system, modulatory synaptic actions function to provide the substrate for a type behavioral modulation.     

In vitro study of rat uterus after chronic formaldehyde exposure.

To measure cholinergic, adrenergic and tryptaminergic receptor activity of formaldehyde (HCHO) in rat uterus, albino rats were treated with 5 and 10 mg/kg, ip HCHO for 30 days. Acetylcholine (ACh) in doses 1.33, 2 and 3 micrograms/ml produced mild to moderate contraction of isolated rat uterus in control group. HCHO had no effect on isolated rat uterus per se, however it reduced ACh and carbachol induced contraction and presence of adrenaline influences in respect of ACh and carbachol activity. Adrenaline per se had no effect in control preparations, but reduced carbachol induced contraction. Propranolol had no effect on rat uterus; but its presence in the bathing medium increased activity of adrenaline. 5-Hydroxytryptamine (5-HT) had no effect of its own on isolated rat uterus but its presence in the bathing medium enhanced contractions of carbachol and oxytocin.     

Effect of isoproterenol on phosphorylase activation in the hyperthyroid rat heart.

Pretreatment of rats for 3 days with triiodothyronine produced an increase in rate in the right atrium and a decrease in force of contraction in the right ventricle and Langendorff heart. Isoproterenol administration produced a time-dependent increase in rate and tension. The increase in rate was consistently greater in atria from hyperthyroid rats, and the increase in tension consistently greater in tissues from euthyroid rats. Isoproterenol also produced a time- and dose-dependent increase in phosphorylase a activity. In the isolated atria and ventricles enzyme activity was similar in the two groups. In the Langendorff hearts, however, there was an enhancement of the isoproterenol-induced increase in phosphorylase activity in hearts from hyperthyroid rats. Reduction of the coronary blood flow to the level found in euthyroid animals did not reduce the potentiation of phosphorylase activation found in hearts from hyperthyroid rats. It is concluded that the potentiation of phosphorylase activation in hearts from hyperthyroid rats is not due to the increase in coronary blood flow.     

The effects of KB-R7943, an inhibitor of reverse Na<Superscript>+</Superscript>/Ca<Superscript>2+</Superscript> exchange,on the force of contraction of papillary muscles in the heart of the ground squirrel <Emphasis Type="Italic">Spermophilus undulatus</Emphasis>

We investigated the effect of KB-R7943, an inhibitor of the reverse mode of Na⁺/Ca²⁺ exchanger, on the force of isometric contractions, the contractile force–frequency relationship and post-rest potentiation (a qualitative parameter of Ca²⁺ levels in sarcoplasmic reticulum) in the right ventricle papillary muscles isolated from ground squirrel hearts during summer (June, n = 4) and autumn (October, n = 4) activities. In the presence of 1.8 mM Ca2+at 36°C, 1–1.5 hours-long treatment of the summer papillary muscles with KB-R7943 produced no significant effects on the contractile indices at the majority of stimulation frequencies. In the autumn papillary muscles KB-R7943 induced a 40–50% decrease in the force of contraction (negative inotropic effect) at low stimulation frequencies (0.1–0.3 Hz) without any significant effect at higher stimulation frequencies (0.4–3.0 Hz). Furthermore, in this group, KB-R7943 suppressed the post-rest potentiation of contractility by 50 ± 21% at pause durations exceeding 120 s. These observations indicate that KB-R7943 can affect Ca²⁺ levels in sarcoplasmic reticulum and that Na⁺/Ca2⁺ exchange may contribute to the physiological remodeling of intracellular Ca²⁺ homeostasis in myocardium of hibernating animals prior their transition to a hypometabolic torpid state.     

ucb 11056, a New Potential Nootropic Drug, Amplifies Induced Cyclic AMP Formation in Rat Brain Tissue

ucb 11056 [2-(4-morpholino-6-propyl-1, 3, 5-triazin-2-yl)aminoethanol] induced a significant (～25%) increase in cyclic AMP levels in different brain areas following its intraperitoneal injection. This effect started as early as 2 min postinjection and lasted for 30 min, after which cyclic AMP levels returned to normal. In hippocampal slice preparations in vitro, ucb 11056 exerted a strong potentiation of cyclic AMP levels when it was combined with agents such as norepinephrine, forskolin, and isoproterenol. Only a slight effect on cyclic AMP levels was measured when ucb 11056 was incubated alone with hippocampal slices. The potentiating effect of ucb 11056 on norepinephrine-stimulated cyclic AMP formation was partially reduced when slices were pretreated with yohimbine and totally abolished when slices were treated with propranolol. These combined data indicate that (a) ucb 11056 rapidly increases cyclic AMP levels in the rat brain in vivo and (b) ucb 11056 potentiates stimulated cyclic AMP formation in vitro. The data also suggest that the central effect of ucb 11056 might be via the modulation of cyclic AMP generation, most probably mediated through adenylate cyclase activation mechanisms combined with a weak inhibitory activity on the cyclic nucleotide phosphodiesterase activity.     

Effects of acetylcholine,physostigmine, and hemicholinium-3 on spontaneous electrical activity of neurosecretory nerves in Carausius and Rhodnius

The neurohaemal, lateral branch of the median nerve in Carausius morosus and the neurohaemal, ventral motor nerve of Rhodnius prolixus are stimulated by acetylcholine to increase the frequency of action potentials recorded via extracellular electrodes from isolated nerves. Physostigmine potentiates electrical activity in both insects and hemicholinium-3 has a depressant effect on Carausius preparations. These results suggests a cholinergic mechanism associated with neurosecretory activity.     

Pharmacological reactivity in cricetus aureus uterus (author's transl)]

The motility of the isolated Cricetus auratus uterus was studied and compared to that of other species. Oxitocyn, epinephrine, norepinephrine, histamine, 5-hydroxy-tryptamine and acetylcholine were used as spasmogen agents. There was not contractil response with epinephrine or nor-epinephrine. Histamine reduced basal tonus. There was contraction with acetylcholine, oxytocin and 5-hydroxy-tryptamine. Cricetus auratus uterus appeared more sensitive when the contraction was registered by the isometric method. No taquifilaxy was produced by 5-hydroxy-tryptamine, as opposed to such effect in rat uterus. The Cricetus auratus uterus has, therefore, shown similar reactivity to that of rat, but different from rabbit and guinea-pig.     

The calcium channel blocker verapamil and cancer chemotherapy

Verapamil is an agent which inhibits the transmembrane flux of calcium ions and is used clinically in the management of cardiac arrhythmias. Combination of this calcium antagonist with antineoplastic agents results in the establishment of chemosensitivity in tumor cells resistant to accepted chemotherapeutic agents and, to a lesser degree, potentiates the efficacy of such compounds in drug-sensitive malignancies. Preliminary indications are that the clinical role of such a potentiation of efficacy would not be limited by an increase in generalized toxicity in non-malignant tissues. Data accumulated indicates a verapamil-induced inhibition of the ability of resistant cells to actively extrude chemotherapeutic agents, possibly due to a decrease in calmodulin activity as a result of a drug-induced alteration of the intracellular calcium environment. The results of preclinical trials to date indicate a role for verapamil in augmenting currently accepted chemotherapeutic regimens.     

Histidine regulation of cyclic AMP metabolism in cultured renal epithelial LLC-PK1 cells.

L-Histidine and imidazole (the histidine side chain) significantly increase cAMP accumulation in intact LLC-PK1 cells. This effect is completely inhibited by isobutylmethylxanthine (IBMX). Histidine and imidazole stimulate cAMP phosphodiesterase activity in soluble and membrane fractions of LLC-PK1 cells suggesting that the IBMX-sensitive effect of these agents to stimulate cAMP formation is not due to inhibition of cAMP phosphodiesterase. Histidine and imidazole but not alanine (the histidine core structure) increase basal, GTP-, forskolin-, and AVP-stimulated adenylate cyclase activity in LLC-PK1 membranes. Two other amino acids with charged side chains (aspartic and glutamic acids) increase AVP-stimulated but neither basal- nor forskolin-stimulated adenylate cyclase activity. This suggests that multiple amino acids with charged side chains can regulate selected aspects of adenylate cyclase activity. To better define the mechanism of histidine regulation of adenylate cyclase, membranes were detergent-solubilized which prevents histidine and imidazole potentiation of forskolin-stimulated adenylate cyclase activity and suggests that an intact plasma membrane environment is required for potentiation. Neither pertussis toxin nor indomethacin pretreatment alter imidazole potentiation of adenylate cyclase. IBMX pretreatment of LLC-PK1 membranes also prevents imidazole to potentiate adenylate cyclase activity. Since IBMX inhibits adenylate cyclase coupled adenosine receptors, LLC-PK1 cells were incubated in vitro with 5'-N-ethylcarboxyamideadenosine (NECA) which produced a homologous pattern of desensitization of NECA to stimulate adenylate cyclase activity. Despite homologous desensitization, histidine and imidazole potentiation of adenylate cyclase was unaltered. These data suggest that histidine, acting via an imidazole ring, potentiates adenylate cyclase activity and thereby increases cAMP formation in cultured LLC-PK1 epithelial cells. This potentiation requires an intact plasma membrane environment, occurs independent of a pertussis toxin-sensitive substrate and of products of cyclooxygenase, and is inhibited by IBMX. This IBMX-sensitive pathway does not involve either inhibition of cAMP phosphodiesterase activity or a stimulatory adenosine receptor coupled to adenylate cyclase.     

In vitro myometrial inhibition by the partitioned aqueous fraction of Anthocleista djalonensis leaves

This study investigated the effect on the uterus of the aqueous fraction of the partitioned methanol crude extract of the leaves of Anthocleista djalonensis (AD) and the possible mechanism of AD activity. AD inhibited the concentration-response curves induced by oxytocin and CaCl2 on the rat uterus in vitro and significantly reduced the EC50 in a concentration-dependent manner (p?< 0.05). A similar effect was observed with salbutamol and verapamil on the concentration-response curves obtained for oxytocin and CaCl2. The inhibitory effect of AD was not attenuated in the presence of propranolol. AD, salbutamol, and verapamil also produced a concentration-dependent relaxation on K+-induced sustained uterine contraction. In Ca2+-free medium, AD and salbutamol similarly inhibited oxytocin-induced contraction, but verapamil failed to produce this effect. The present results suggest that AD, being a mixture of phytochemicals, probably exerts inhibitory activity on in vitro uterine contractions of the nonpregnant, diethylstilboestrol-treated rat by multiple mechanisms that do not involve interaction with β-adrenergic receptors and do not solely depend on inhibition of calcium influx.     

Effect of thyrotropin-releasing hormone on rat myometrium

The effect of TRH in vitro was observed on electromyograms and isometric tension changes in the uterine horn isolated from the rat. TRH induced transient prolongation of the duration of spike bursts in the electromyogram and an increased tension in contraction of diestrous uterine horns. No distinct response to TRH was elicited in preparations from rats during other estrous stages. TRH produced a contraction associated with a burst of spike potentials in the quiescent horn from the estrogen-primed ovariectomized rat. Priming with progesterone was not a prerequisite for responsiveness to TRH. In a medium with a high Ca concentration, diestrous uteri were quiescent but a transient contraction associated with a burst of spike potentials was induced by TRH. In a Ca-free medium, TRH failed to elicit any response in the diestrous uterus but acetylcholine induced a contraction without associated spike potentials. It appears that TRH stimulates Ca-influx into the uterine muscle in which responsiveness is dependent on estrogen priming.     

Adrenomedullin inhibits the contraction of cultured rat testicular peritubular myoid cells induced by endothelin-1

The present study documents that adrenomedullin (AM), a vasoactive peptide originally identified in pheochromocytoma tissue and present in the testis, in vitro affects the function of testicular peritubular myoid cells (TPMC), a contractile cell type located in the seminiferous tubule wall. AM stimulated cAMP production by cultured TPMC taken from 16-day-old rats, and this effect was completely inhibited by the AM antagonist AM-(22-52) and partially by the CGRP (calcitonin gene-related peptide) antagonist CGRP-(8-37). Studies on TPMC contractile activity documented that AM inhibits TPMC contraction induced by endothelin-1 (ET-1) and that its effect is antagonized by AM-(22-52). Neutralizing AM produced by TPMC with the addition of anti-AM antibody induced a significant increase of ET-1-induced contraction. When exposed to the protein kinase A inhibitor H-89, AM inhibitory activity on ET-1-induced TPMC contraction was suppressed, whereas the nitric oxide synthase inhibitor N:(G)-nitro-L-arginine methyl esther did not modify AM activity. In conclusion, our study indicates that AM stimulates cAMP production and inhibits the contraction induced by ET-1 in TPMC in vitro, and that AM produced by TPMC has an autocrine effect. We propose that AM may have a role in the control of seminiferous tubule contraction.     

Somatostatin potentiates cholinergic neurotransmission in ferret trachea

We studied the effect of somatostatin on contractile responses to electrical field stimulation (EFS) in isolated ferret tracheal segments. Somatostatin (up to 10(-5) M) did not change resting tension, but it potentiated the contractile response to EFS dose dependently, with a maximum effect at 10(-6) M. Thus, at a concentration of 10(-6) M, somatostatin significantly decreased the mean log of EFS frequency producing 50% of maximum contraction from a control value of 0.52 +/- 0.07 to 0.24 +/- 0.06 (SE) Hz (P less than 0.01). The potentiating effect of somatostatin (10(-6) M) was not inhibited by hexamethonium, indomethacin, BW755C, pyrilamine, methysergide, or D,Pro2,D,Trp7,9-SP, but it was inhibited by atropine or by the somatostatin antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]. In contrast to EFS-induced contraction, contractions produced by acetylcholine (10(-9) to 10(-3) M) were not affected by somatostatin at a concentration of 10(-6) M. These results suggest that somatostatin potentiates contractions produced by EFS via presynaptic cholinergic mechanisms and probably through a specific somatostatin receptor.