Nonneural components in the response of fresh human airways to electric field stimulation

Fresh human bronchi, obtained at thoracotomy and maintained at 37 degrees C, were studied in vitro to investigate their response to electric field stimulation (EFS). We found complex responses that were not only composed of a rapid initial nerve-mediated cholinergic contraction and a non-adrenergic nerve-mediated relaxation, but, in 80% of preparations, also of a tonic contraction with a sustained time course. This sustained phase was not blocked by the nervous conductance blocker tetrodotoxin (TTX) and was therefore not neurally mediated. Controlled transient cooling to 4 degrees C in the organ bath reduced this sustained phase selectively for several hours. The leukotriene (LT) antagonist FPL 55712, dexamethasone, which inhibits phospholipase A2, and the antiasthmatic drug cromolyn all reduced the sustained phase significantly. In 20% of strips, an additional TTX-resistant contraction was seen directly after the cholinergic phase. This contraction could be inhibited by indomethacin. A similar small peak sometimes appeared after selective blocking of either the cholinergic or the sustained phases. Experiments in which the epithelium was removed from the strips suggested that this indomethacin-sensitive response, but not the sustained phase, was dependent on the presence of epithelium. These results show that EFS of fresh human bronchi stimulated cholinergic and nonadrenergic inhibitory nerves and gave rise to a partly epithelium-dependent synthesis of arachidonic acid metabolites, which caused contractile responses that interfered with the neurally mediated responses.     

Inhibition by VIP and atriopeptin II on the field stimulation evoked release of [3H]noradrenaline in the rat portal vein.

The modulatory effects of vasodilatory peptides on noradrenaline release from sympathetic nerve terminals have been studied in the rat portal vein model. Transmural field stimulation of the longitudinally mounted vein preparation evoked concomitant increases in the [3H]noradrenaline overflow and the integrated tension. Both responses were abolished by guanethidine or tetrodotoxin, whereas only the tension response was blocked by phentolamine. CGRP and VIP, both being present in intramural nerve fibers in the rat portal vein, were compared with atriopeptin II for modulatory effects. CGRP (100 nM) had no effect on the overflow of [3H]noradrenaline or the integrated tension response to transmural stimulation. VIP (30 nM) and atriopeptin II (30 nM) both caused significant reductions of both [3H]noradrenaline overflow and the integrated tension. These results indicate that the decreased tension response to transmural stimulation in the presence of VIP or AP II reflects the sum of both pre- and postsynaptic inhibitions.     

Vasoactive intestinal polypeptide (VIP) inhibits neurally evoked smooth muscle activity of rat uterine cervix in vitro

VIP inhibits the spontaneous motor activity (including tone) in isolated preparations of uterine cervix from oophorectomized rats, but has no direct effect on preparations from estrogen-treated animals. Electrical field stimulation of nerves in the tissue evokes a contractile response that is inhibited by VIP in a concentration-dependent manner. The neuronal link probably involves a cholinergic mechanism, since the contraction is blocked by atropine. The results suggest the presence of VIP receptors both in cholinergic nerves and in smooth muscle cells of the rat uterine cervix.     

神经降压素对刺激下丘脑减压区所致减压反应的影响

大鼠下丘脑前部一侧减压区,采用直流方波或化学刺激、注射微量神经降压素及其抗血清和放射免疫分析等方法,探讨了神经降压素对刺激该减压区所致减压反应的影响。结果表明：（１）电或化学刺激该减压区,可出现同其它哺乳动物相似的减压反应;（２）该减压区注射微量神经降压素,可使电刺激该减压区所致的减压反应明显增强;反之,注射抗神经降压素血清,该减压反应明显抑制;（３）电刺激该减压区,可使下丘脑和血浆中的神经降压素免疫活性物含量明显增高。结果提示,神经降压素可能参与电刺激该减压区所致的减压反应过程。     

Canine neurotensin, neurotensin6-13 and neuromedin N: primary structures and receptor activity

Canine neurotensin (NT) and neuromedin N (NMN) were isolated from extracts of ileal mucosa using radioimmunoassay for detection. The structures determined were consistent with those predicted by earlier cDNA work. The molar ratio of NT to NMN was ca. 7, suggesting that the NT/NMN precursor, which contains one copy of each peptide, undergoes complex posttranslational processing or that other NT-precursors lacking NMN exist. In addition to NT, small quantities of NT6-13 and NT2-13 were obtained. Native and synthetic preparations of these peptides were indistinguishable in a radioreceptor assay employing rat brain membranes and 125I-labeled NT; NT6-13 was ca. 8-times more potent than NT and NMN was about one-sixth as potent as NT. NT6-13 was also ca. 10 times more potent than NT in inhibiting spontaneous contractile activity in longitudinally-oriented smooth muscle strips of porcine jejunum. Preparations of intestinal N-cells as well as N-cell vesicles also appeared to contain NT2-13 and NT6-13; however, it is not yet clear whether these peptides are utilized physiologically or simply represent metabolites of NT. These results suggest that further work on the processing of NT precursor and on biologic abilities of partial sequences of NT could be fruitful.     

Removal of the epithelium potentiates acetylcholine in depolarizing canine bronchial smooth muscle

Experiments were designed to determine whether the airway epithelium affects the membrane potential of the underlying smooth muscle. The effect of epithelium removal (by gentle rubbing) on the responsiveness of isolated canine bronchi was studied. Simultaneous recordings of mechanical and electrical activity were made in paired circumferential strips (with and without epithelium) of third-order bronchi. Changes in tension were recorded with a force transducer, and changes in membrane potential were measured with a microelectrode. The cell membrane potential and resting tension of the bronchial smooth muscle were stable over a 150-min period and were not affected by removal of the epithelium. In the presence of antagonists at muscarinic and adrenergic receptors, the resting tension and membrane potential were comparable in preparations with and without epithelium. By contrast, the anticholinesterase, echothiophate, caused depolarization in bronchi without epithelium. Exposure to high potassium induced similar levels of depolarization and contraction in tissues with and without epithelium. No significant differences in threshold for depolarization or for mechanical activation in the membrane potential-tension relationship were noted in the presence or absence of epithelium. In the presence of echothiophate, removal of the epithelium augmented the contraction of the bronchi to acetylcholine; the depolarization of the cell membrane induced by the cholinergic transmitter was significantly larger than in control tissues, even when matched contractions were compared. These observations indicate that the respiratory epithelium generates an inhibitory substance that dampens depolarization and contraction of bronchial smooth muscle caused by acetylcholine.     

Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig

Summary The occurrence and distribution of peptide-containing nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)- and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP- and CGRP-immunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP- and neurokinin A (NKA)-like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A non-cholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.     

Inhibition of cholinergic neurotransmission in human airways by beta 2-adrenoceptors

The purpose of the study was to determine whether catecholamines modulate cholinergic neurotransmission in isolated human airway smooth muscle. Bronchial rings were suspended in organ baths for isometric measurement of tension, and contractions were induced by either electrical field stimulation (EFS) or exogenous acetylcholine (ACh). Isoproterenol, epinephrine, and norepinephrine in that order of potency produced concentration-dependent inhibition of comparable responses to EFS and ACh. However a potency difference of 100-fold for isoproterenol (IC50 = 4.80 X 10(-8) M for EFS and 3.70 X 10(-6) M for ACh) and 10-fold for both epinephrine and norepinephrine was observed for inhibition of responses to EFS compared with responses to ACh. The inhibitory effects of isoproterenol on responses to EFS were prevented by propranolol and ICI 118551 (a beta 2-antagonist) but not by betaxolol (a beta 1-antagonist). Tyramine had no effect on contractions elicited by EFS. These experiments demonstrate that beta-agonists inhibit cholinergic nerve-induced contractions of human bronchi more potently than contractions induced by exogenous ACh, suggesting modulation of cholinergic neurotransmission by prejunctional beta 2-receptors.     

Functional innervation of the myometrium of Myotis lucifugus, the little brown bat

Myometria of pregnant and nonpregnant Myotis lucifugus were studied in vitro by using electrical field stimulation as well as autonomic agonists and antagonists to determine whether functional responses corresponded with structural evidence showing abundant adrenergic and sparse cholinergic innervation, which uniquely does not disappear during pregnancy. Field stimulation (70 V, 0.6 ms, 5.0-s pulse train, 2.5 - 60 Hz) of myometria from nonpregnant (hibernating) bats produced graded responses consisting of an initial alpha-adrenergic contraction and a subsequent beta-adrenergic relaxation phase. Responses were sensitive to both the nerve poison tetrodotoxin and the adrenergic antagonist guanethidine, demonstrating that they resulted from stimulation of intrinsic adrenergic nerves. Field stimulation responses were unaffected by atropine indicating that there was no functional cholinergic innervation, even though carbachol-induced contraction showed that muscarinic receptors were present. In contrast, functional innervation of cervical tissue was cholinergic and nonadrenergic-non-cholinergic, but not adrenergic. At the beginning of active gestation, some myometrial preparations exhibited little of no response to field stimulation. However, as uterine size increased, the biphasic response to field stimulation was enhanced, particularly the inhibitory (beta-adrenergic) phase. Moreover, the contractile phases, though reduced, was not abolished by alpha-adrenergic antagonists. The residual contractile response was also tetrodotoxin-resistant, suggesting that the myometrium was sensitive to direct electrical stimulation. Near the end of pregnancy, myometrial tissue became nonresponsive to both field stimulation and autonomic agonists, suggesting an absence of available receptor sites on muscle cells.     

Prejunctional beta 1-adrenoceptors inhibit cholinergic transmission in canine bronchi

The aim of the present study was to determine in canine bronchi the effects produced by norepinephrine (released from adrenergic nerve terminals) on cholinergic neurotransmission. Electrical stimulation of canine bronchi activates cholinergic and adrenergic nerve fibers. The adrenergic neuronal blocker, bretylium tosylate, inhibited the increase in [3H]norepinephrine overflow evoked by electrical stimulation but did not prevent that caused by the indirect sympathomimetic tyramine. During blockade of the exocytotic release of norepinephrine with bretylium, the pharmacological displacement of the sympathetic neurotransmitter by tyramine significantly decreased the contractions evoked by electrical stimulation but did not affect contractions caused by exogenous acetylcholine. Metoprolol, a beta 1-adrenergic antagonist, abolished and propranolol significantly reduced the effect of tyramine during electrical stimulation. alpha 2-Adrenergic blockade, beta 2-adrenergic blockade, or removal of the epithelium did not significantly affect the response to tyramine. These results suggest that norepinephrine when released from sympathetic nerve endings can activate prejunctional inhibitory beta 1-adrenoceptors to depress cholinergic neurotransmission in the bronchial wall.     

Stimulation of phosphatidylinositol turnover in various tissues by cholinergic and adrenergic agonists, by histamine and by caerulein

Studies are reported of the biochemical and pharmacological characteristics of the stimulation of phosphatidylinositol metabolism that is produced in appropriate target tissues by stimulation of various receptors that use Ca(2+) as their second messenger. (1) Muscarinic cholinergic and alpha-adrenergic phosphatidylinositol responses were observed in rat lacrimal gland, and a response to caerulein was detected in the longitudinal smooth muscle of guinea-pig ileum. (2) The muscarinic cholinergic phosphatidylinositol response of rat lacrimal gland, like that of several other tissues, is not dependent on the availability of extracellular Ca(2+). (3) Three phosphatidylinositol responses, namely to histamine in guinea-pig ileum smooth muscle, to alpha-adrenergic stimulation in rat vas deferens and to muscarinic cholinergic stimulation in rat lacrimal gland, were all found to involve phosphatidylinositol breakdown. (4) The stereospecificity of the muscarinic receptor responsible for the phosphatidylinositol response of guinea-pig pancreas was tested by using the two stereoisomeric forms of acetyl-beta-methylcholine; the S-isomer was very much more active than the R-isomer in provoking both phosphatidylinositol breakdown and its labelling with (32)P, as it is in provoking other physiological responses such as contractility or secretion. (5) Pilocarpine, a muscarinic partial agonist, provoked a significantly smaller phosphatidylinositol breakdown in rat parotid fragments than did carbamoylcholine, a potent muscarinic agonist. (6) All of these results are consistent with, but do not prove, a previously offered hypothesis that suggests that phosphatidylinositol breakdown is a reaction essential to stimulus-response coupling at a variety of cell-surface receptors that mobilize Ca(2+) from and through the plasma membranes of target tissues.     

Galanin potentiates electrical stimulation and exogenous norepinephrine-induced contractions in the rat vas deferens

In order to evaluate the mode of action of galanin (GAL) on the neuroeffector mechanism of peripheral sympathetic nerve fibers, the effects of this peptide were tested on the electrical stimulated and the unstimulated preparations of the isolated rat vas deferens in the presence of 10(-7) M atropine. The contractile responses, which were mediated predominantly by activation of postganglionic noradrenergic nerve fibers were dose-dependently potentiated by GAL in concentrations ranging from 1 to 50 nM. The facilitatory action induced by GAL in high concentrations (greater than 10 nM) usually returned to the control level at 2-3 min and were tachyphylactic. The potentiating action of GAL was not modified by pretreatment with 10(-7) M propranolol. Contractions produced by exogenous norepinephrine (NE) in the unstimulated preparations were not affected by pretreatment with low concentrations (less than 5 nM) of GAL. On the other hand, the contractions were dose-dependently potentiated 1 min after pretreatment with higher concentrations (greater than 10 nM) of GAL, which recovered 15 min after constant flow washout. Contractions developed by exogenous 5-hydroxytryptamine were not affected, or slightly inhibited, by GAL (1-50 nM). In some preparations without electrical stimulation, high concentrations of GAL caused a slight contraction, which was not blocked by pretreatment with 10(-6) M phentolamine and 10(-6) M tetrodotoxin. These results suggest that GAL receptors exist presynaptically in the rat vas deferens and that stimulation of the receptors by GAL potentiates the release of NE from the nerve terminals during postganglionic sympathetic nerve stimulation. Other mechanisms for GAL action, such as influence on neuronal uptake and catecholamine metabolism, cannot be ruled out.     

Effect of streptozotocin diabetes on motor and inhibitory transmission in rat anococcygeus.

The effect of streptozotocin diabetes of 4-week duration on the adrenergic motor transmission and on the nonadrenergic, noncholinergic, inhibitory transmission in the rat anococcygeus was investigated by recording contractile and relaxant activity of isolated muscle preparations taken from diabetic and age-matched control animals. The neurogenic contractile responses to electrical field stimulation were significantly reduced in the preparations from diabetic rats. The inhibitory transmission remained unaffected in the diabetic rats. Concentration--response curves showed no change in sensitivity of the diabetic anococcygei to noradrenaline. The maximum tension generated was also similar in preparations from diabetic and nondiabetic animals. The contractile responses to electrical field stimulation were significantly greater in preparations from diabetic rats treated for 4 weeks with either sorbinil (20 mg.kg-1.day-1 orally) or myo-inositol (667 mg.kg-1.day-1 orally) when compared with the untreated diabetic controls; the sensitivity to noradrenaline was identical in all three groups. It is concluded that streptozotocin diabetes causes a significant reduction of adrenergic contractile responses of the anococcygeus to electrical field stimulation by a prejunctional mechanism, and the reduction can be prevented by treating the animals with the aldose reductase inhibitor sorbinil or with myo-inositol.     

Adenosine selectively inhibits noncholinergic transmission in guinea pig bronchi

The neuromodulatory action of adenosine and ATP was investigated in isolated guinea pig bronchial strip chain preparations contracted with electrical field stimulation. The tissues were placed in organ baths containing physiological salt solution and stimulated at 8-Hz frequency, 0.5-ms pulse duration, and 30 V (approximately 100 mA) for 5 s. Electrical field stimulation evoked a biphasic contraction of bronchial muscle, consisting of an initial contraction followed by a sustained contraction, which was mediated by intramural cholinergic and noncholinergic nerve stimulations, respectively. Adenosine, at concentrations greater than M, caused a concentration-dependent inhibition in the height of the noncholinergically mediated contraction, accompanied by a very weak inhibition on the cholinergically mediated response. ATP (10(-5) to 3 x 10(-3) M) also produced a similar inhibitory effect on the noncholinergically mediated contraction, but the inhibitory potency was less than that of adenosine. The inhibitory response to adenosine was enhanced by the pretreatment with dipyridamole (2 x 10(-6) M) but antagonized with aminophylline (10(-5) M). Contractions of bronchial muscle evoked by exogenous acetylcholine (2 x 10(-6) M) or substance P (2 x 10(-7) M) were significantly inhibited by the adenosine (3 x 10(-4) M) pretreatment. These data suggest that in isolated guinea pig bronchi adenosine selectively inhibits noncholinergic neurotransmission through prejunctional P1-purinoceptors.     

Pain and neurotransmitters

1. To study physiological roles of substance P (SP), gamma-aminobutyric acid (GABA), enkephalins and other endogenous substances, we developed several kinds of isolated spinal cord preparations of newborn rats. 2. In these preparations, various slow responses of spinal neurons evoked by stimulation of primary afferent C fibers were depressed by a tachykinin antagonist, spantide. These results together with many other lines of evidence suggest that SP and neurokinin A serve as pain transmitters in a subpopulation of primary afferent C fibers. 3. Some C-fiber responses in various isolated spinal cord preparations were depressed by GABA, muscimol, and opioid peptides. In contrast, bicuculline (GABA antagonist) and naloxone (opioid antagonist) potentiated the "tail pinch potential," i.e., a nociceptive response of the ventral root evoked by pinch stimulation of the tail in isolated spinal cord-tail preparation of the newborn rat. The latter results support the hypothesis that some primary afferents activate inhibitory spinal interneurons which release GABA and enkephalins as transmitters to modulate pain inputs.     

Prejunctional inhibitory muscarinic receptors on cholinergic nerves in human and guinea pig airways

We have investigated whether prejunctional inhibitory muscarinic receptors ("autoreceptors") exist on cholinergic nerves in human airways in vitro and whether guinea pig trachea provides a good model for further pharmacological characterization of these receptors. Pilocarpine was used as a selective agonist and gallamine as a selective antagonist of these autoreceptors. Acetylcholine (ACh) release from postganglionic cholinergic nerves was elicited by electrical field stimulation (EFS) (40 V, 0.5 ms, 32 Hz). In human bronchi, pilocarpine inhibited the contractile response to EFS in a dose-related fashion; the dose inhibiting 50% of the control contraction was 2.2 +/- 0.4 x 10(-7) (SE) M (n = 22), and the inhibition was 96% at 3 x 10(-5) M. The inhibitory effects of pilocarpine were antagonized by gallamine in a dose-related fashion. The results were qualitatively the same in the guinea pig. Gallamine significantly enhanced the contractile response to EFS in the guinea pig, whereas pirenzepine failed to do so, which suggests that M2-receptors are involved. We conclude that prejunctional muscarinic receptors that inhibit ACh release are present on cholinergic nerves in human airways and that guinea pig trachea is a good model for further pharmacological characterization of these receptors, which appear to belong to the M2-subtype.     

Impairment of contractility associated with muscarinic supersensitivity in trachea isolated from diabetic rats: lack of correlation with ultrastructural changes or quinuclidinyl benzylate binding to lung membranes

Evolution of cholinergic response of rat isolated trachea was determined after various durations of diabetes (17, 40, 90, 150 and 210 days). Long-term diabetes was associated with both impairment of contractility and supersensitivity to cholinergic stimulation. However, the mechanism of these alterations remains to be determined, as response to field stimulation was not specifically altered while electron microscopy studies could not detect any significant change in the aspect of nerves, smooth muscle or epithelium. As well, binding studies of lung cholinergic receptors using the antagonist ligand [³H]-quinuclidinyl benzylate and the agonist carbachol did not detect any change in diabetic animals.     

The effects of substance P and met5-enkephalin in dog ileum

Substance P initiated tonic contraction of dog ileum when administered in doses from 1 pg to 20 micrograms intraarterially (ED50 = 67 ng). Low doses acted to excite cholinergic postganglionic neurones since atropine or tetrodotoxin (TTX) increased the ED50 of substance P about 25-fold, while hexamethonium and local field stimulation had only a small effect to increase the ED50. Also atropine and tetrodotoxin effects were not additive. Higher doses apparently acted to stimulate smooth muscle directly, but no evidence was obtained that local field stimulation could release substance P to act on smooth muscle. Substance P tachyphylaxis prevented substance P actions on cholinergic nerves, but it did not affect responses to intraaterial acetylcholine or block distal inhibition from proximal distention or field stimulation. Met-enkephalin given intraarterially, was also excitatory in doses from 1 ng to 20 micrograms; the amplitude of tonic and phasic contractions produced was significantly decreased by TTX and atropine but was not diminished by hexamethonium or substance P tachyphylaxis. Partial tachyphylaxis to met-enkephalin was produced but was not diminished by hexamethonium or substance P tachyphylaxis. Partial tachyphylaxis to met-enkephalin was produced without affecting the ED50 for substance P. We conclude that substance P acts in small amounts on receptors in myenteric nerves to release acetylcholine by a mechanism, presumably involving postganglionic cholinergic nerves, while met-enkephalin also apparently may act at least in part through a similar TTX- and atropine-sensitive mechanism. These peptides also caused activation of other receptors, probably on smooth muscle by noncholinergic. TTX-insensitive mechanisms. Also the receptors for each peptide which are located on nerves were distinct and independent since tachyphylaxis could be produced to each without affecting the response to the other.     

A dose-response study of forskolin, stimulatory hormone, and guanosine triphosphate analog on adenylate cyclase from several sources

We have described relationships involving forskolin stimulation of adenylate cyclase (AC) from a variety of sources and the potentiation of forskolin effects by stimulatory hormones (glucagon, ACTH, and epinephrine) and beta, gamma-imidoguanosine 5'-triphosphate (Gpp(NH)p). The effects on AC were examined using membrane preparations of rabbit adipocytes, rat adipocytes, rat erythrocytes, and rat liver. Also examined was the AC of liver membranes of rat pretreated with pertussis toxin as well as that solubilized from rat liver membranes. Maximal forskolin stimulation of AC in all preparations studied revealed a consistent 10-fold increase in AC activity. The EC50 for forskolin was 10 microM for rat liver, 15 microM for rabbit and rat adipocytes and 17 microM for rat erythrocyte AC stimulation. In all cases the AC activity attained by forskolin stimulation was further enhanced by stimulatory hormones in a dose-dependent manner. Furthermore, a combination of all three activators (forskolin, stimulatory hormone, and Gpp(NH)p) resulted in an even greater overall stimulation to levels ranging from 25- to 30-fold over unstimulated activity levels. In the presence of saturating levels of each stimulatory hormone and Gpp(NH)p, the EC50 for forskolin diminished markedly to the range of 0.5 to 4.0 microM. In the absence of any apparent tissue specificity for forskolin stimulation, the general pattern of these results further implicates the catalytic site of the AC complex as the site of forskolin activation. Furthermore, activation of additional components of the complex by Gpp(NH)p and tissue specific hormones may further influence the AC activity and thereby potentiate the stimulation by forskolin.     

Studies of kinin-like properties of a new peptide isolated from bovine brain]

Kinin-like properties of two new peptides NRP-11 and P7 which have structural similarity with neurotensin (NT) and kallidin (K) were investigated. It was found that, unlike NT and K, the new peptides possess reduced myotropic and hypotensive activity. On the other hand, similarly to NT and K, the new peptides exhibited a high histamine-releasing activity in rat peritoneal mast cells. Possible central effects are implied for peptide NRP-11 isolated from bovine brain and its fragment P7.