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J S Gillespie

Publications and source records attributed to J S Gillespie.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of NG-substituted analogues of L-arginine on NANC relaxation of the rat anococcygeus and bovine retractor penis muscles and the bovine penile artery.

1. The effects of two inhibitors of nitric oxide synthase, NG-monomethyl L-arginine (L-NMMA) and NG-nitro L-arginine (L-NOARG), were examined on non-adrenergic non-cholinergic (NANC) inhibitory transmission in the rat anococcygeus, bovine retractor penis (BRP) and bovine penile artery. 2. In the rat anococcygeus, L-NMMA (10-1000 microM) produced a concentration-dependent augmentation of guanethidine (30 microM)-induced tone and inhibited NANC relaxation at all frequencies tested (0.1-20 Hz): the maximum inhibition obtained was 56 +/- 6% (n = 6). L-NOARG (0.3-30 microM) also augmented tone and inhibited NANC relaxation in a concentration-dependent manner, but unlike L-NMMA the maximum inhibition was 100%. 3. In the BRP, L-NMMA (10-100 microM) had no effect on tone or NANC-induced relaxation, but at 1000 microM tone was increased and NANC relaxation inhibited by 25 +/- 7% (n = 6). L-NOARG (0.3-30 microM) produced a concentration-dependent increase in tone and inhibition of NANC relaxation. As in the rat anococcygeus, inhibition of NANC relaxation was complete. 4. The effects of L-NMMA and L-NOARG were stereospecific since D-NMMA (10-1000 microM) and D-NOARG (1-1000 microM) had no effect on tone or NANC relaxation of the rat anococcygeus or BRP. 5. L-Arginine (10-300 microM) had no effect by itself on NANC-induced relaxation of the rat anococcygeus or BRP. It did, however, reverse the ability of L-NMMA (10-1000 microM) to augment tone and inhibit NANC relaxation in the rat anococcygeus and BRP. 6. On the bovine penile artery, both L-NMMA (100 microM) and L-NOARG (30 microM) augmented the tone induced by guanethidine (30 microM) and 5-hydroxytryptamine (0.2 microM) in an endothelium-dependent manner. L-NMMA had no effect on NANC-induced relaxation, but inhibited acetylcholine-induced endotheliumdependent relaxation. L-NOARG abolished NANC relaxation at all frequencies tested and inhibited acetylcholine-induced relaxation. D-NOARG (30 microM) had no effect on NANC or acetylcholine-induced relaxation. 7. The ability of L-NOARG to abolish NANC-induced relaxation in the rat anococcygeus, BRP and bovine penile artery suggests that the L-arginine-nitric oxide pathway mediates neurotransmission in all three tissues. The effectiveness of L-NMMA in blocking NANC relaxation-in the rat anococcygeus but not the BRP and bovine penile artery suggests a species difference in the neuronal nitric oxide synthase. The neuronal and endothelial nitric oxide synthases in the penile artery also appear to differ.

Animals↗
PubMed1990

The effects of pyrogallol and hydroquinone on the response to NANC nerve stimulation in the rat anococcygeus and the bovine retractor penis muscles.

1. The effects of pyrogallol and hydroquinone on the bovine retractor penis (BRP) and rat anococcygeus muscles to non-adrenergic, non-cholinergic (NANC) nerve stimulation have been examined. Both drugs at a concentration of 10(-4) M significantly reduced the response in the rat anococcygeus muscle but had no effect in the BRP muscle. 2. The inhibition of the NANC response in the rat anococcygeus muscle by pyrogallol was completely reversed by superoxide dismutase suggesting it was due to the generation of superoxide anions. 3. Pyrogallol inhibited the response to nitric oxide (NO) in the rat anococcygeus muscle but not that to 3-isobutyl-1-methyl-xanthine (IBMX) which confirmed a selective action. 4. These results suggest that the NANC neurotransmitter in the rat anococcygeus muscle is susceptible to superoxide anions and may be NO or a substance that can liberate NO.

1-Methyl-3-isobutylxanthine↗
PubMed1989

A comparison of haemoglobin and erythrocytes as inhibitors of smooth muscle relaxation by the NANC transmitter in the BRP and rat anococcygeus and by EDRF in the rabbit aortic strip.

1. The inhibitory effect of erythrocyte suspensions and haemoglobin solutions on the response of the bovine retractor penis muscle (BRP) and the rat anococcygeus to field stimulation of their non-adrenergic non-cholinergic (NANC) nerves has been compared. Haemoglobin 3 microM greatly reduced the relaxant response in both tissues whereas a haemoglobin-equivalent suspension of erythrocytes was without effect. 2. A similar comparison of erythrocytes and haemoglobin on the response of the rabbit aortic strip to EDRF liberated by acetylcholine (ACh) showed that both reduced EDRF-mediated relaxation, though haemoglobin was significantly more effective. 3. These results suggest that the NANC transmitter may not be as freely diffusible through the erythrocyte membrane as EDRF and may therefore not be nitric oxide.

Acetylcholine↗
PubMed1989

The effects of L-arginine and NG-monomethyl L-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation.

The effect of the competitive inhibitor of L-arginine, NG-monomethyl L-arginine (L-NMMA) on the response of the rat anococcygeus muscle to non-adrenergic, non-cholinergic (NANC) inhibitory nerve stimulation has been examined. L-NMMA causes a rise in muscle tone and inhibition of the response to nerve stimulation. The stereoisomer D-NMMA is without effect. The rise in tone and inhibition of the nerve response is reversed by L-arginine. Another analogue, L-canavanine, which is effective against L-arginine utilization in the macrophage, was without effect on the rat anococcygeus. These results provide indirect evidence for nitric oxide (NO) or a substance releasing NO as the transmitter of the NANC nerves in this tissue.

Animals↗
PubMed1988

The lack of involvement of cyclic nucleotides in the smooth muscle relaxant action of BRL 34915.

1. The relaxant effect of BRL 34915 has been examined on four isolated preparations, the bovine retractor penis (BRP), guinea-pig taenia coli, guinea-pig trachea and rabbit aortic strip contracted by either histamine, carbachol, noradrenaline or 10 mM KCl. Even though the probability of the involvement of external calcium entering through voltage-operated channels in these tissues varied, there was little corresponding variation in sensitivity to BRL 34915. 2. The relaxant effect of BRL 34915 on the BRP and guinea-pig taenia coli was unaffected by haemoglobin 3.3 microM or Apamin 0.5 microM, concentrations which blocked completely the relaxant effect of non-adrenergic, non-cholinergic (NANC) nerve stimulation in these tissues. 3. BRL 34915 in doses causing maximum relaxation did not increase the levels of either cyclic AMP or cyclic GMP in the BRP, although the appropriate enzymes were present and could be stimulated by forskolin or sodium nitroprusside. 4. In the BRP isoprenaline 30 microM acting through beta-receptors caused maximum relaxation but did not raise the levels of cyclic AMP, even though lower doses of 2 microM did raise the levels of this nucleotide in the rabbit uterus. 5. These results provide some indirect evidence that membrane hyperpolarization may not be the only cause of the smooth muscle relaxation induced by BRL 34915. However, neither a rise in cyclic AMP nor cyclic GMP are satisfactory alternative mechanisms.

Animals↗
PubMed1988

Influence of haemoglobin and erythrocytes on the effects of EDRF, a smooth muscle inhibitory factor, and nitric oxide on vascular and non-vascular smooth muscle.

1. The relaxant action of endothelium-derived relaxing factor (EDRF), the smooth muscle inhibitory factor (IF) isolated from the bovine retractor penis (BRP), nitric oxide (NO) and sodium nitroprusside (NaNP) on four vascular and non-vascular smooth muscle preparations has been examined. Their sensitivity to EDRF, the IF and NO was the same, suggesting all might be NO. Sodium nitroprusside produced complete relaxation of the rat anococcygeus at low doses, suggesting an action additional to the intracellular release of NO. 2. Haemoglobin added to solutions of EDRF, activated IF or NO completely removed their relaxant properties, consistent with all three acting by virtue of NO. 3. Suspensions of red blood cells with a haemoglobin concentration equivalent to to that used in the previous experiments were as effective as haemoglobin in abolishing the relaxant effect of EDRF or NO but were ineffective against the activated IF. 4. The similarity in sensitivity of a series of smooth muscles and the binding by haemoglobin are consistent with NO being the active principle of both EDRF and the acid activated IF. The abolition of the effect of EDRF by red blood cells (RBCs) is further confirmation for this hypothesis, but the ineffectiveness of RBCs against acid-activated IF suggests that either the latter is not NO or that it is bound in a way which makes it unable to diffuse through cell membranes.

Animals↗
PubMed1986

A comparison of the action of the endothelium-derived relaxant factor and the inhibitory factor from the bovine retractor penis on rabbit aortic smooth muscle.

The dependence of relaxation of rabbit aortic strips by carbachol and by the inhibitory factor from the bovine retractor penis (BRP) on the presence of endothelium has been compared. Carbachol-induced relaxation is abolished by removing the endothelium, inhibitory factor-induced relaxation is unimpaired. The inhibitory factor, therefore, does not act by releasing an endothelium-derived relaxing factor (EDRF). The effect of inhibitors of eicosanoid metabolism on relaxation was examined. Quinacrine and nordihydroguaiaretic acid abolished the relaxant effect of carbachol and flurbiprofen had no effect. The relaxation produced by the inhibitory factor was unaffected by quinacrine and flurbiprofen while nordihydroguaiaretic acid potentiated the response. No eicosanoid appears, therefore, to be involved in the relaxant effect of the inhibitory factor from the BRP. Methylene blue, a drug reported to inhibit guanylate cyclase, in a concentration of 10 microM selectively abolished the relaxation produced by carbachol. However, at the higher concentration of 30 microM it abolished almost completely the response to inhibitory factor from the BRP and reduced inhibition by sodium nitroprusside. It is not possible from these results to exclude the possibility that the EDRF and the inhibitory factor from the BRP are chemically related.

Animals↗
PubMed1984

Release of noradrenaline and dopamine by nerve stimulation in the guinea-pig and rat vas deferens.

Spontaneous and nerve stimulated release of noradrenaline and dopamine from rat and guinea-pig vas deferens have been measured electrochemically after separation by high performance liquid chromatography (h.p.l.c.). In the absence of nerve stimulation both noradrenaline (NA) and dopamine were released into the bathing fluid in the rat but in the guinea-pig only noradrenaline could be detected. Drugs which block neuronal and extraneuronal uptake of catecholamines had little effect on spontaneous overflow but both tetraethylammonium and phenoxybenzamine increased overflow. Transmural nerve stimulation (5-10 Hz) increased catecholamine overflow in both species and dopamine release was now measurable from the guinea-pig vas. In the rat, the proportion of dopamine to NA was unchanged from that released spontaneously. The release of both amines was little affected by drugs that block neuronal and extraneuronal uptake and a monoamine oxidase inhibitor, but was inhibited by tetrodotoxin 0.2 microgram ml-1. In the guinea-pig tetraethylammonium 10 mM doubled overflow and phenoxybenzamine 10(-5)M increased it by five times but the dopamine percentage remained constant and equal to the control. Following nerve stimulation the amount of dopamine released expressed as a percentage of total catecholamine release was 6% for the rat and 1.3% for the guinea-pig. These values were considerably higher than the comparable figures for dopamine: NA content of the two tissues (2% and 0.5% respectively). Repeated periods of stimulation depleted these tissue stores and the depletion of dopamine was significantly greater than that of NA. 6 Our interpretation of these results is that both dopamine and NA are released from a common store during normal noradrenergic transmission. While all or most of the axonal dopamine is contained in this releasable pool, most of the axonal NA lies in a second, less readily released pool.

Animals↗
PubMed1983

The effect of an inhibitory factor from the bovine retractor penis on the gastro-intestinal tract and gall bladder of the guinea-pig.

1 The effect of a smooth muscle inhibitory factor extracted from the bovine retractor penis has been examined on a variety of in vitro smooth muscle preparations from the guinea-pig alimentary canal and on the guinea-pig gall bladder. 2 The inhibitory factor caused relaxation of spontaneous and carbachol-induced tone in the taenia coli, the stomach fundal strip and the duodenum and colon. There was little effect on the ileum. Sensitivity was highest in the taenia coli where the response to the inhibitory factor mimicked the response to stimulation of the non-adrenergic, non-cholinergic (NANC) inhibitory nerves. 3 In the taenia coli the inhibitory response to stimulation of the NANC nerves and to ATP was abolished by apamin 5 x 10(-8) M, whereas this or higher concentrations had no effect on the response to the inhibitory factor. This makes it unlikely that the latter is the neurotransmitter in these NANC nerves. 4 The inhibitory factor had no effect on the gall bladder. Inhibitory responses to field stimulation were obtained in this tissue but these were insensitive to tetrodotoxin in concentrations greater than those needed to block the motor cholinergic nerves.

Adenosine Triphosphate↗
PubMed1983

The contractile response to and the release of noradrenaline by transmural nerve stimulation in the guinea-pig vas deferens and a comparison with the response to noradrenaline.

The release of noradrenaline from the guinea-pig vas deferens by transmural stimulation was measured electrochemically after separation by h.p.l.c. Variations in release with different durations of stimulation were then compared with the mechanical response during stimulation. During long periods of 270 s of stimulation at 10 Hz the average release of noradrenaline in the final 250 s remained at about 50% of that released during the first 20 s yet the mechanical response throughout the later time declined to near zero. Superfusion with constant concentrations of noradrenaline produced mechanical responses similar to those from transmural nerve stimulation, an initial rapid contraction declining to a low level of maintained activity. During the later period, when the response to infused noradrenaline was low, the twitch response to transmural stimulation was potentiated. Phentolamine 10(-6)M reduced the potentiation of the twitch response to transmural stimulation by noradrenaline and propranolol 10(-6)M enhanced the potentiation. These results suggest that the decline in the adrenergic component of the response to prolonged transmural nerve stimulation is not the result of a decline in noradrenaline release but mainly due to desensitization to the contractile effect of noradrenaline. Since the similar desensitization produced by infused noradrenaline does not reduce the twitch response to transmural nerve stimulation it is unlikely that the transmitter responsible for that component is noradrenaline.

Animals↗
PubMed1983

Neurogenic vasodilatation in isolated bovine and canine penile arteries.

Field stimulation of isolated, perfused bovine or canine penile arteries produced dilatation, after the adrenergic motor component of the response had been blocked with guanethidine and the vessels had developed a background tone. The vasodilatation was blocked by tetrodotoxin but not by atropine. The vasodilator responses to field stimulation were compared with those produced by ATP, by vasoactive intestinal peptide (VIP), and by the inhibitory factor extracted from the bovine retractor penis muscle. Of the three putative transmitters, the inhibitory factor produced responses that most closely resembled those to field stimulation. Haemoglobin, which blocks non-adrenergic, non-cholinergic inhibitory transmission in the bovine and canine retractor penis muscles, did not impair the vasodilatations produced by ATP or VIP, but slowly reduced or abolished those produced by field stimulation or by the inhibitory factor. Haemoglobin itself produced a powerful constriction of the isolated penile arteries. The results are compatable with the possibility that the inhibitory factor from the bovine retractor penis muscle (which may be the inhibitory transmitter in that muscle) is, or closely resembles, the transmitter of non-adrenergic, non-cholinergic vasodilator fibres in the penile arteries of dog and ox.

Adenosine Triphosphate↗
PubMed1982

The effect of ethanol on inhibitory and motor responses in the rat and rabbit anococcygeus and the bovine retractor penis muscles.

1 Ethanol (200 mM) reduced the response to inhibitory nerve stimulation in the rat and rabbit anococcygeus and the bovine retractor penis (BRP) muscles. Ethanol also reduced the response to the inhibitory extract from the BRP consistent with the inhibitory factor in these extracts playing some part in the response to inhibitory nerve stimulation. 2 Ethanol's effect on the response to other inhibitory stimuli was examined in the rabbit anococcygeus and the BRP. In the anococcygeus the response to carbachol was reduced, to bradykinin and isobutylmethylxanthine (IBMX) unaltered, and to isoprenaline and adenosine 5'-triphosphate (ATP) potentiated. In the BRP responses to IBMX and sodium nitroprusside were unaltered but in this tissue the response to isoprenaline was reduced. Ethanol's ability to reduce inhibitory responses is, therefore, selective and confined to inhibitory nerve stimulation, inhibitory extract, carbachol, and, in the BRP, isoprenaline. 3 Ethanol reduced the rate of development of inhibition even where the magnitude of the inhibitory response was unaltered. 4 In the rat anococcygeus, ethanol (200 mM) potentiated the response to motor nerve stimulation and to noradrenaline (NA) at low frequencies and low concentrations respectively. Higher ethanol concentrations (400 mM) reduced the response to both motor nerve stimulation and NA. The motor response to carbachol was also reduced. 5 Ethanol (200 mM) itself caused an easily reversible contraction in all three tissues. This was not due to the release of NA but was highly sensitive to the removal of external calcium from the medium. 6 A unified explanation of these varied effects of ethanol based on a reduction in membrane binding of calcium and a reduced efficiency of receptor coupling is suggested.

Animals↗
PubMed1982

Block of some non-adrenergic inhibitory responses of smooth muscle by a substance from haemolysed erythrocytes.

1. A preparation of haemolysed rat erythrocytes (the haemolysate) blocked the relaxations of both the bovine retractor penis and the rat anococcygeus muscles in response to field stimulation of their non-adrenergic inhibitory nerves. The effective concentration range was 5-20 mul./ml. of haemolysate, equivalent to 0.25-1.0 mul./ml. of blood. The active principle in the haemolysate was a non-dialysable, heat-labile material of molecular weight between 50,000 and 100,000 daltons. If, as appeared probable, the active component of the haemolysate was oxyhaemoglobin, its effective blocking concentration was 0.5-2 muM.2. Haemolysate (5-20 mul./ml.) also blocked the relaxation of both the bovine retractor penis and the rat anococcygeus to the inhibitory factor extracted from the bovine retractor penis, an observation supporting the possibility that this inhibitory factor may be the transmitter released by the inhibitory nerves in these tissues. In the bovine retractor penis, haemolysate was also effective in blocking relaxations in response to sodium nitroprusside, but relaxations produced by prostaglandin E(1) or isobutylmethylxanthine were unchanged or only slightly reduced.3. In contrast, in the taenia of the guinea-pig caecum, haemolysate did not block the non-adrenergic inhibitory response to field stimulation, nor the relaxation produced by ATP, although it did block the relaxation produced by the inhibitory factor.4. In spiral strips of isolated rabbit aorta, haemolysate (10 mul./ml.) increased the contraction produced by noradrenaline and blocked the relaxation produced by the inhibitory factor. These were shown to be independent effects.5. Apamin, which blocked the relaxation of the taenia of the guinea-pig caecum elicited by either ATP or field stimulation of its non-adrenergic nerves, was without effect on relaxations of the bovine retractor penis or rat anococcygeus muscles in response to field stimulation of inhibitory nerves or to inhibitory factor.6. These differences in the blocking effects of apamin and haemolysate suggest either that the transmitter in the bovine retractor penis and rat anococcygeus differs from that in the guinea-pig taenia, or, if the transmitter is the same, then its mechanism of action differs.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Dopamine and noradrenaline levels in peripheral tissues of several mammalian species.

Tissue levels of dopamine (DA) and noradrenaline (NA) have been compared in atrium, spleen, mesenteric artery, vas deferens and renal cortex of sexually mature rats, guinea-pigs, ferrets, rabbits and cats. The results suggest the presence of dopaminergic autonomic axons in the cat renal cortex, as has been previously reported for the dog. Such nerves are probably sparse or absent in the kidneys of the other species examined.

Animals↗
PubMed1981

Actions on the cardiovascular system of an inhibitory material extracted from the bovine retractor penis.

1 A partially purified material has been isolated from methanol extracts of the bovine retractor penis muscle. This material exerts biological activity only after treatment with acid and subsequent neutralisation. The active principle in this extract, which appears to be no known autacoid, mimics the response to stimulation of the non-adrenergic, non-cholinergic nerves in the bovine isolated retractor penis muscle. 2 This inhibitory extract did not alter the heart rate or blood pressure of the anaesthetized rat when administered either by intravenous or intra-arterial injection, nor did it have any obvious effect on isolated cardiac muscle. 4 The extract produced relaxation of spiral strips of various arteries isolated from ox, cat, rabbit or rat, in which tone was induced by noradrenaline, K+ of Ba2+. 5 The extract also produced dilatation of the resistance vessels of the rat isolated mesenteric circulation and the rat hindquarters perfused with Krebs solution; tone was induced in these vessels by adrenaline or noradrenaline. 6 Lack of vasodilator activity of the extract in the whole animal appeared to be due to rapid inactivation in the blood, probably by binding to the erythrocytes.

Anesthesia↗
PubMed1981

Some physical and chemical properties of the smooth muscle inhibitory factor in extracts of the bovine retractor penis muscle.

1. A method of extracting and partially purifying a smooth muscle inhibitory factor from the bovine retractor penis is described. This consists of extraction in methanol followed by adsorption on an anion exchange resin, elution from the resin with 500 mM-sodium chloride solution and, if necessary, removal of adenine nucleotides by adsorption on alumina. 2. The inhibitory factor exists in a stable pharmacologically inactive form and an unstable pharmacologically active form. Conversion to the active form is by a brief exposure to acid at pH 2.0. 3. The inhibitory factor is insoluble in ether or acetone but soluble in methanol. Anhydrous methanol, however, irreversibly destroys pharmacological activity especially if the inhibitory factor is in the active form. This effect of methanol is prevented by the presence of 20-30-% water. 4. The inhibitory factor binds to an anion exchange resin but not to a cation exchange resin. It can be eluted from the resin by 500 mM-sodium chloride solution. 5. The molecular weight of the inhibitory factor, as judged by the ability to pass ultrafiltration membranes, is about 500. 6. Inhibitory activity is unaffected by the proteases trypsin, subtilisin or pepsin or by leucine aminopeptidase, pyroglutamate aminopeptidase or carboxypeptidase. The inhibitory effect of the extract and the inhibitory response to stimulation of the non-adrenergic, non-cholinergic nerves are also unaffected by the protease inhibitor, aprotinin. The active material, therefore, is unlikely to be a peptide. 7. Inhibitory activity is abolished by exposure of the extracts to periodic acid or sodium periodate. Acetic anhydride in pyridine also abolishes activity but the vehicle pyridine is also effective. 8. Sodium borohydride but not borate abolishes inhibitory activity when added to the acid-activated material at pH 2.0 but has no effect or may even potentiate activity if added to the stable inactive form at pH 9.0. When added to the acid-activated but neutralized material at pH 6.8 it usually abolishes inhibitory activity but occasionally has no effect. 9. These results suggest the smooth muscle inhibitory factor in these extracts is potent and probably novel. It does not appear to be a peptide or a lipid but may contain a carbohydrate as part of the molecule. Its possible physiological role is discussed.

Animals↗