The primary structures and myotropic activities of two tachykinins isolated from the African clawed frog,Xenopus laevis

Two peptides with limited structural similarity to mammalian substance P (SP) and neurokinin A (NKA) have been isolated from extracts of the intestine of the African clawed frog (Xenopus laevis). The primary structure of an SP-like peptide was established as: Lys-Pro-Arg-Pro-Asp-Gln-Phe-Tyr-Gly-Leu-Met.NH(2), which is identical to the previously characterized peptide, bufokinin isolated from the toad Bufo marinus. The primary structure of an NKA-related peptide was established as Thr-Leu-Thr-Thr-Gly-Lys-Asp-Phe-Val-Gly-Leu-Met.NH(2). Only the five amino acids at the C-terminal region of the peptide are identical to mammalian NKA whereas the N-terminal region shows no structural similarity to previously characterized tachykinins. Immunohistochemical investigations of the gut wall revealed a dense network of nerve fibres and nerve cell bodies containing SP/NKA-like substances. The myotropic effects of the Xenopus tachykinins were compared with the contractile effect of mammalian SP and NKA on isolated strips of circular smooth muscle from Xenopus stomach. No significant differences in potencies (-log EC(50)) or in intrinsic activities were observed between the Xenopus and mammalian peptides. The potencies for the Xenopus SP-like (8.49+/-0.15) and the NKA-like peptide (8.12+/-0.06) were similar suggesting that the amino acid sequence at the N-terminal region of the tachykinins is not important in activating the tachykinin receptors in Xenopus gastric smooth muscle. The maximum response to Xenopus SP (alpha=0.59+/-0.06) was significantly lower than to the NKA-like peptide (alpha=1.0) suggesting a more effective interaction of the NKA-like peptide with the tachykinin receptor(s) in Xenopus stomach.     

Contraction of guinea pig trachea by epidermal growth factor--urogastrone

To evaluate further the action of epidermal growth factor - urogastrone (EGF-URO) in smooth muscle systems, we examined the effect of the peptide on guinea pig tracheal strips. The cumulative addition of EGF-URO to the organ bath resulted in a concentration-dependent tonic contraction without tachyphylaxis. The half-maximal contraction was obtained at 13 +/- 3 ng/mL EGF-URO (2 nM). The maximum contraction at 100 ng/mL approached 60% of that induced by 1 microM histamine. No significant difference in the EGF-URO-induced contraction was observed in the presence or absence of a functional epithelium. Preincubation with 1 microM indomethacin for 20 min abolished the action of EGF-URO. The contractile effect of EGF-URO was not affected by yohimbine, propranolol, atropine, tetrodotoxin, and esculetin. However, mepacrine caused inhibition by 37 +/- 7% (mean +/- SEM for n = 3). Verapamil (10 microM) inhibited the EGF-induced response by 62 +/- 5% (mean +/- SEM for n = 4); the response was also absent in Ca-free (1 mM EGTA) buffer. However, the response was restored after the readdition of calcium. Our results suggest that EGF-URO can modulate tracheal smooth muscle contractility via a cyclooxygenase product and raise the possibility that EGF-URO might play a role in controlling pulmonary smooth muscle tone in vivo.     

Tensiometric study of muscular strips of guinea pig gallbladder

The tensiometric properties of smooth muscle strips from 10 male guinea pig gallbladders were evaluated following acetylcholine (ACH), cholecystokinin octapeptide (CCK-OP), cerulein (CRL) and histamine (HIS) administration. All agonists induced dose-dependent tonic contractions with the maximum effect caused by the octapeptide. CRL showed a 9-folds higher relative potency when compared to CCK-OP. ED50s of agonists were: ACH 1.36 +/- 0.28 SEM microM (n = 14; range 0.20-3.60); HIST, 5.7 +/- 1.9 microM (n = 12; range 1-23); CRL 0.72 +/- 0.15 nM (n = 8; range 0.35-1.07); CCK-OP, 6.77 +/- 1.80 nM (n = 12; range 0.44-20.32); For the same strips, max tension (g), was: 1.97 (SEM 0.12) for ACH; 1.5 (0.18) for HIST; 1.81 (0.18) for CRL; 2.44 (0.14) for CCK-OP. Pretreatment of the strips with atropine (1 microM) completely abolished ACh-induced contractions, without affecting either CCK-OP or CRL responses. The model represents a valid "in vitro" study of different molecules whose action might stimulate, enhance or inhibit the physiological hormonal and non-hormonal effect of the agonists at the level of animal and human gallbladder smooth muscle.     

Purification, structural characterization, and myotropic activity of a peptide related to des-Arg(9)-bradykinin from an elasmobranch fish, the little skate, Leucoraja erinacea

A bradykinin (BK)-related peptide was isolated from heat-denaturated plasma from an elasmobranch fish, the little skate, Leucoraja erinacea after incubation with porcine pancreatic kallikrein. The primary structure of the peptide (H-Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe-OH; skate BK) shows limited structural similarity to the mammalian B1 receptor agonist, des-Arg(9)-BK. The myotropic activities of synthetic skate BK, and the analog skate [Arg(9)]BK, were examined in isolated skate vascular and intestinal smooth muscle preparations. Skate BK produced a concentration-dependent constriction of the mesenteric artery (EC(50)=4.37x10(-8)M; maximum response=103.4+/-10.23% of the response to 60mM KCl) but the response to skate [Arg(9)]BK was appreciably weaker (response to 10(-6)M=73.0+/-23.4% of the response to 60mM KCl). Neither the first branchial gill arch nor the ventral aorta responded to either purified peptide. Skate BK also produced a concentration-dependent constriction of intestinal smooth muscle preparations (EC(50)=2.74x10(-7)M; maximum response 31.0+/-12.2% of the response to 10(-5)M acetylcholine). Skate [Arg(9)]BK was without effect on the intestinal preparation. The data provide evidence for the existence of the kallikrein-kinin system in a phylogenetically ancient vertebrate group and the greater potency of skate BK compared with the analog skate [Arg(9)]BK suggests that the receptor mediating vascular responses resembles the mammalian B1 receptor more closely than the B2 receptor.     

Hepatic clearance of somatostatin and gastrin-releasing peptide

In order to examine hepatic clearance of gastrointestinal regulatory peptides, rat livers were perfused in situ, and radiolabelled somatostatin (S-14, S-28), gastrin-releasing peptide (GRP-14, GRP-27), and vasoactive intestinal peptide (VIP) were injected into the portal vein and hepatic venous effluent was collected. S-14 and S-28 were not affected significantly by hepatic transit: 91.6 +/- 2.8% (SEM) of S-14 and 95.9 +/- 2.2% of S-28 were recovered, and neither peptide was degraded by hepatic transit, as determined by immunoprecipitation and gel chromatography. GRP-14 and GRP-27 were also not affected by hepatic transit: 91.5 +/- 1.6% of GRP-14 and 94.4 +/- 2.4% of GRP-27 were recovered intact. In contrast, when radiolabelled VIP was infused into the portal vein, 56.7 +/- 7.4% of injected labelled VIP appeared in the hepatic venous effluent, of which only 33.5 +/- 1.2% was intact peptide. Results of these studies indicate that enteric VIP released into the splanchnic/portal circulation is cleared by hepatic transit. However, somatostatin and GRP peptides appear to traverse the liver intact and could potentially produce systemic biological effects.     

Microvascular and macrovascular endothelial cells produce different constrictor substances.

The media from cultured microvascular and macrovascular endothelial cells (conditioned media, CM) were collected and tested for constrictor activity in sheep coronary artery rings and tracheal smooth muscle strips in vitro (isometric force), expressed as percentage of contraction produced by 80 mM KCl. Both microvascular (micro) and macrovascular (macro) CM caused a sustained slow-onset contraction (P less than 0.05) of the coronary artery rings by 71 +/- 10% (micro; n = 7) and 67 +/- 8% (macro; n = 6) and tracheal smooth muscle strips by 33 +/- 14% (micro; n = 6) and 34 +/- 6% (macro; n = 11); the calcium antagonist gallopamil (10(-7) M) attenuated these effects by 25-55%. Unconditioned medium and medium conditioned by cultured tracheal smooth muscle cells had no constrictor activity on coronary artery rings or tracheal smooth muscle strips. Synthetic endothelin (ET-1) also produced contraction of coronary artery rings and tracheal smooth muscle strips. The mean levels of ET-1 measured by radioimmunoassay were 1,200 pg/ml in the macro CM and 33 pg/ml in the micro CM. Depleting macro CM of ET-1 by affinity columns constructed with protein A agarose and anti-ET-1 antibody removed the contractile activity for coronary artery rings and tracheal smooth muscle strips. Thus ET-1 did not appear to be the contractile substance in the micro CM. Preliminary characterization of the contractile substance in micro CM revealed that it was heat stable, had a molecular weight of less than 10,000, was inactivated by trypsin, and retained its activity after two cycles of freeze-thawing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastrin-releasing peptide stimulates cholecystokinin secretion in perfused rat duodenum

We examined the effect of porcine gastrin-releasing peptide (GRP-27) and other analogous neuropeptides on cholecystokinin (CCK) secretion from the isolated perfused rat duodenum. GRP-27 stimulated CCK secretion in a monophasic pattern and in a dose-dependent manner ranging from 10(-9) M to 10(-6) M, and 10(-7) M of GRP-27 led to an increment of 442 +/- 120.8 fmol/3 min. The stimulatory effect of GRP-27 on CCK was not inhibited by 10(-5) M of atropine. 10(-7) M of neuromedin C and B, analogs of GRP, stimulated CCK secretion to increments of 382 +/- 64.1 and 289 +/- 47.2 fmol/3 min, respectively. Carbachol (10(-9) to 10(-6) M), VIP (10(-9)M), secretin (10(-9)M) and glucose (11 mM) did not stimulate CCK secretion, and the addition of atropine (10(-5)M) to them led to no significant changes. These results suggest that GRP may directly stimulate CCK secretion from the duodenum and work as a non-cholinergic, peptidergic neurotransmitter.     

Anti-inflammatory and utero-relaxant effects in human myometrium of new generation phosphodiesterase 4 inhibitors

The anti-inflammatory and utero-relaxant effects of two potent phosphodiesterase 4 (PDE4) inhibitors of the latest generation: cilomilast (one of the most advanced PDE4 inhibitors in clinical development, reportedly more selective for PDE4D) and compound A (which displays 12-fold greater selectivity toward PDE4B and/or PDE4A than toward PDE4D) were evaluated in human uterine smooth muscle. We first established that these compounds exhibit greater efficacy in inhibiting total cAMP-PDE activity in pregnant versus nonpregnant myometrium (E(max) = 78.0% +/- 3.6% and 80.3% +/- 2.2% in pregnant versus 57% +/- 4.7% and 70.5% +/- 5.9% in nonpregnant women for compound A and cilomilast, respectively; P < 0.05 for both compounds), confirming the prominent participation of PDE4 isoforms in cAMP hydrolysis in the near-term pregnant myometrium. Using pregnant myometrial explants, we have shown that both these drugs and also rolipram, the prototype PDE4 inhibitor, produce concentration-dependent inhibition of lipopolysaccharide (LPS) induced tumor necrosis factor alpha (TNFalpha) release with similar potency in each case (pD2 = 8.0 +/- 0.5, 7.9 +/- 0.2, and 7.6 +/- 0.2 for compound A, cilomilast, and rolipram, respectively). The maximum inhibition produced is 65%. Pretreatment with forskolin or 8-bromo-cAMP mimics the PDE4 inhibitor effect. Furthermore, compound A and cilomilast both produce concentration-dependent inhibition of the spontaneous contractions of myometrial strips and are more potent in pregnant than in nonpregnant myometrium (pD2 = 7.3 +/- 0.7 and 8.1 +/- 0.3 in pregnant versus 6.2 +/- 0.9 and 6.6 +/- 0.1 in nonpregnant myometrium for compound A and cilomilast, respectively; P < 0.05 for both compounds). This demonstrates that the PDE4 isoforms involved in the mechanism of contraction are different in the pregnant and nonpregnant myometrium. Our study highlights the importance of developing PDE4 inhibitors for the pharmacological management of infection-induced preterm labor.     

Comparison of the actions of bombesin, gastrin-releasing peptide-27, neuromedin B, and gastrin-releasing peptide-10 in causing release of gastrin and gastric inhibitory peptide in rats

The objective of this study was to compare the gastrin- and gastric inhibitory peptide (GIP)-releasing actions of bombesin, gastrin-releasing peptide (GRP)-27, neuromedin B, and GRP-10 in rats. Both bombesin and GRP-27 are potent stimulants of gastrin and GIP release, whereas neuromedin B and GRP-10 are less effective, on a molar basis.     

The effect of gastrin-releasing peptide on the endocrine pancreas

The 27-amino acid peptide gastrin releasing peptide (GRP-(1–27)) was infused at 4 dose levels (0.01, 0.1, 1.0, and 10 nM) into the arterial line of the isolated perfused porcine pancreas. Infusions were performed at 3 different perfusate glucose levels (3.5, 5.0, and 8.0 mM) and at two levels of amino acids (5 and 15 mM). GRP-(1–27) stimulated insulin and pancreatic polypeptide secretion and inhibited somatostatin secretion in a dose-dependent manner. Glucagon secretion was unaffected by infusion of GRP under all circumstances. The effect of GRP-(1–27) on insulin secretion was enhanced with increasing perfusate glucose levels, whereas the effects upon somatostatin and pancreatic polypeptide secretion were independent of perfusate glucose levels. The responses to GRP were unaffected by elevation of the concentration of amino acids in the perfusate. The effects of GRP were unaffected by atropine at 10⁻⁶ M. The localization of GRP within the porcine pancreas, its release during electrical stimulation of the vagus nerve, and its potent effects upon pancreatic endocrine secretion make it conceiveable that the peptide participates in parasympathetic regulation of pancreatic endocrine secretion.     

Gastrin releasing peptide-29 evokes feeding responses in the rat

In mammals, gastrin releasing peptide (GRP) 10 and 27 reduce food intake. In the current work, we test the hypothesis that GRP-29, the large molecular form of GRP in the rat, also evokes feeding responses consistent with a possible role in satiety. Here, we measured three feeding responses, size of first meal, intermeal interval (IMI, time between first and second meal) and satiety ratio (SR, satiation period for every unit of food consumed in the first meal), in overnight food deprived rats following GRP-10, 27 or 29 (0, 0.3, 1.0, 2.1, 4.1, 10.3, 17.2 nmol/kg) intraperitoneally and presentation of a 10% sucrose test diet. GRP-29 and GRP-27 reduced the size of the first meal, prolonged IMI and increased SR, but GRP-10 failed to exhibit similar feeding responses. The order of potency was GRP-29 = GRP-27 > GRP-10. The current data support a role for GRP-29 in the short-term regulation of food intake.     

The synthesis and structure-activity relationships of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel opener targeted for urge urinary incontinence

A series of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones was prepared and shown by electrophysiological analysis to activate a cloned maxi-K channel mSlo (or hSlo) expressed in Xenopus laevis oocytes. The effects of these structurally novel maxi-K channel openers on bladder contractile function were studied in vitro using isolated rat bladder strips pre-contracted with carbachol. Several 1,3-diaryl 1,2,4-(4H)-triazol-5-one derivatives were found to be potent smooth muscle relaxants but this activity did not completely correlate with maxi-K channel opening.     

Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle

Botulinum toxin injection into the pylorus is reported to improve gastric emptying in gastroparesis. Classically, botulinum toxin inhibits ACh release from cholinergic nerves in skeletal muscle. The aim of this study was to determine the effects of botulinum toxin on pyloric smooth muscle. Guinea pig pyloric muscle strips were studied in vitro. Botulinum toxin type A was added; electric field stimulation (EFS) was performed every 30 min for 6 h. ACh (100 microM)-induced contractile responses were determined before and after 6 h. Botulinum toxin caused a concentration-dependent decrease of pyloric contractions to EFS. At a low concentration (2 U/ml), botulinum toxin decreased pyloric contractions to EFS by 43 +/- 9% without affecting ACh-induced contractions. At higher concentrations (10 U/ml), botulinum toxin decreased pyloric contraction to EFS by 75 +/- 7% and decreased ACh-induced contraction by 79 +/- 9%. In conclusion, botulinum toxin inhibits pyloric smooth muscle contractility. At a low concentration, botulinum toxin decreases EFS-induced contractile responses without affecting ACh-induced contractions suggesting inhibition of ACh release from cholinergic nerves. At higher concentrations, botulinum toxin directly inhibits smooth muscle contractility as evidenced by the decreased contractile response to ACh.     

Effect of cholecystokinin octapeptide and somatostatin on the motility of guinea pig and canine gallbladder

Species differences have been observed in the effect of cholecystokinin octapeptide (CCK OP) on the canine and guinea pig gallbladder smooth muscle motility. 1. CCK OP was more potent stimulant in canine than in guinea pig gallbladder smooth muscles. Its pD2 values were 10 and 9.2, respectively. 2. The acetylcholine (10(-4) M)-induced maximum contractions in canine gallbladder muscle strips were by 50% lower as compared to the CCK OP (10(-8) M) maximum responses while in guinea pig gallbladder muscle strips the acetylcholine (ACh) maximum responses were by 20% lower than the CCK OP maximum responses. 3. CCK OP increased [3H]ACh release by 27% in canine gallbladder and by 40% in guinea pig gallbladder. 4. Somatostatin (SOM) had not any direct myogenic effect in guinea pig and canine gallbladder but it decreased [3H]ACh release from gallbladder intrinsic cholinergic neurons.     

Evidence for the involvement of myoendothelial gap junctions in EDHF-mediated relaxation in the rat middle cerebral artery

The mechanisms underlying endothelium-dependent hyperpolarizing factor (EDHF) in the middle cerebral artery (MCA) remain largely unresolved. In particular, very little is known regarding the way in which the signal is transmitted from endothelium to smooth muscle. The present study tested the hypothesis that direct communication via myoendothelial gap junctions contributes to the EDHF response in the male rat MCA. EDHF-mediated dilations were elicited in rat MCAs by luminal application of ATP or UTP in the presence of Nomega-nitro-L-arginine methyl ester and indomethacin. Maximum dilation to luminal ATP (10(-4) M) was reduced significantly after incubation with a gap peptide cocktail (9 +/- 4%, n = 6) compared with a scrambled gap peptide cocktail (99 +/- 1%, n = 6, P < 0.05). A gap peptide cocktail had no effect on amplitude of endothelial cell hyperpolarization in response to 3 x 10(-5) M UTP (22 +/- 3 vs. 22 +/- 1 mV, n = 4), whereas smooth muscle cell hyperpolarization was significantly attenuated (17 +/- 1 vs. 6 +/- 1 mV, n = 4, P = 0.004). Connexin (Cx) 37 was localized to smooth muscle and Cx43 to endothelium, whereas Cx40 was found in endothelium and smooth muscle. Electron microscopy revealed the existence of frequent myoendothelial junctions. The total number of myoendothelial junctions per 5 microm of MCA sectioned was 2.5 +/- 0.5. Our results suggest that myoendothelial communication contributes to smooth muscle cell hyperpolarization and EDHF dilation in male rat MCA.     

Neuronal cholecystokinin,gastrin-releasing peptide,neurotensin, and β-endorphin in the intestine of the guinea pig

Summary The guinea-pig intestine was found to harbor nerve fibers containing immunoreactive cholecystokinin (CCK), gastrin-releasing peptide (GRP), neurotensin or - endorphin. Such fibers occurred in the myenteric and submucous ganglia and in the smooth muscle. GRP- and CCK-fibers, in addition, were found in the mucosa. Following colchicine treatment, neuronal perikarya in the myenteric ganglia displayed CCK-, GRP-, or -endorphin immunoreactivity. CCK-immunoreactive perikarya were located also in the submucous ganglia. Neurotensin-immunoreactive cell bodies could not be detected. The presence of immunoreactive neuronal perikarya in intramural ganglia indicates that CCK-, GRP- and -endorphin-containing fibers are intrinsic to the gut wall. GRP, neurotensin, and -endorphin were identified in extracts of smooth muscle by immunochemical and Chromatographic analysis.CCK-8, GRP and neurotensin contracted the isolated taenia coli. Tetrodotoxin reduced the response to CCK-8 but not that to GRP and neurotensin, suggesting that the two latter peptides act directly on smooth muscle receptors. The effect of CCK-8 is partly mediated by cholinergic nerves, since not only tetrodotoxin but also atropine greatly reduced the CCK-8-induced contractile response. The substance P (SP) antagonist, (d-Pro², d-Trp^7,9)-SP_1–11 had no effect on the CCK-8-induced contraction of the taenia. CCK-8 enhanced the SP-mediated (atropine-resistant) contractile response to electrical stimulation but not that mediated by acetylcholine. -Endorphin had no effect on the tension of the muscle but reduced the response to electrical stimulation (cholinergic as well as SP-mediated) through a naloxone-sensitive mechanism.While CCK-8 and -endorphin seem to play neuromodulatory roles in the taenia coli, the significance of GRP and neurotensin remains enigmatic.     

Minimal ligand analysis of gastrin releasing peptide. Receptor binding and mitogenesis

Gastrin releasing peptide (GRP) is a peptide hormone containing 27 amino acids which is structurally analogous to the amphibian peptide bombesin. GRP serves a variety of physiological functions and has been implicated in the pathophysiology of small cell lung cancer. Previous work has demonstrated that the modified C terminus of GRP, N-acetyl-GRP-20-27, exerts full agonist activity in a variety of assay systems. However, no systematic comparison of binding of GRP fragments to its receptor and mitogenic potency has been reported. To investigate whether smaller GRP fragments could bind to the GRP receptor without stimulating mitogenesis, we performed binding inhibition and thymidine uptake assays with Swiss 3T3 fibroblasts. These studies were facilitated by the development of a novel tritiated GRP-based radioligand, [3H-Phe15] GRP-15-27, which exhibits enhanced chemical stability compared to iodinated GRP derivatives. We examined a series of C-terminal GRP fragments, from the pentapeptide to the octapeptide, with both N-acetyl and free amine moieties at the N terminus. N-Acetylated derivatives were more potent than their primary amine counterparts in both assays. Deletion of N-terminal residues from GRP-20-27 resulted in significant loss of potency in both assays: the EC50 values of N-acetyl-GRP-21-27 were 10(2)-fold higher than N-acetyl-GRP-20-27, those of N-acetyl-GRP-22-27 were 10(4)-fold higher, and N-acetyl-GRP-23-27 showed minimal activity at concentrations below 100 microM. These results suggest that 1) both His20 and Trp21 play an important role in binding of GRP to the receptor, and 2) for this series of N-terminal deletions, binding to the receptor and mitogenic activity are tightly coupled.     

Gastrin releasing peptides increase Fos-like immunoreactivity in the enteric nervous system and the dorsal vagal complex

We and others have shown that gastrin-releasing peptide (GRP) reduces food intake. In this study, we determined the activation of the gastrointestinal and dorsal vagal complex (DVC) neurons by various forms of GRP to determine the pathway involved in this reduction. We found the following: (1) GRP-10, -27 and -29 (2.1 nmol/kg, i.p.) increased the Fos-like immunoreactivity (Fos-LI, a marker for neuronal activation) in the myenteric neurons of the stomach and the area postrema (AP) of the DVC; (2) GRP-27 and GRP-29 increased the Fos-LI in the myenteric plexus of the duodenum; and (3) only GRP-29 increased the Fos-LI in the submucosal plexus of the duodenum. In conclusion, GRP may reduce food intake by activating the area postrema. The enteric neurons may have a potential role in this reduction through the direct activation of the AP or exerting local gut actions, such as the stimulation of gut motility or secretions.     

A comparison of the contractile activity of PGD2 and PGF2 alpha on human isolated bronchus

Prostaglandins may be implicated in the bronchoconstriction which occurs in asthma. Prostaglandins F2 alpha (PGF2 alpha) and D2 (PGD2) have been reported to produce bronchoconstriction in asthmatic subjects in vivo and PGF2 alpha contracts human isolated airway smooth muscle. We examined the relative efficacy and potency of PGF2 alpha and PGD2 on human bronchial spiral strips taken from 6 patients at thoracotomy. PGF2 alpha had greater efficacy than PGD2. The mean % Tmax (percentage of maximal contractile response) +/- s.e. mean were 84 +/- 7 and 54 +/- 7 respectively (P less than 0.05). PGF2 alpha (mean pD2 +/- s.e. mean = 6.39 +/- 0.6) tended to be more potent than PGD2 (5.68 +/- 0.2). Since, in vivo, PGD2 has greater efficacy and potency than PGF2 alpha, our results suggest that the in vivo effect of these prostaglandins does not result solely from an action on airway muscle.     

Neuronal localization and motor effects of gastrin-releasing peptide (GRP) in rat uterus

All parts of the internal female reproductive tract of the rat contained nerve fibers with immunocytochemically visible gastrin-releasing peptide (GRP)-like material. GRP-like immunoreactivity was also seen in nerve cell bodies of the paracervical ganglion formation, which in addition, harboured GRP nerve fibers. Pharmacological experiments were performed on isolated uterine and cervical smooth muscle tissue from two groups of spayed animals, one of which received estradiol. Both GRP and its non-mammalian counterpart, bombesin, evoked concentration-dependent clonic contractions in uterus and cervix, most pronounced in the estrogen-treated animals. Bombesin induced a stronger contractile force than GRP. The responses were not affected by tetrodotoxin. The observations suggest that GRP may be one of several neural messengers involved in the control of uterine motor activity.