PubMed Health⌕ Search

Biomedical subjects

L Stjärne

Publications and source records attributed to L Stjärne.

At least 19 recordsLinked to original sources
PubMed1992

Electrophysiological and electrochemical analysis of the secretion of ATP and noradrenaline from the sympathetic nerves in rat tail artery: effects of alpha 2-adrenoceptor agonists and antagonists and noradrenaline reuptake blockers.

The aim of this study was to investigate whether or not nerve impulses release ATP and noradrenaline in parallel from the sympathetic nerve terminals of the rat tail artery. The extracellularly recorded excitatory junction current (EJC) was used to study, pulse by pulse, the release of ATP. An electrochemical method was used to study online the nerve stimulation-induced rise in the extracellular concentration of endogenous noradrenaline at the probe, a carbon fibre electrode (CF). This parameter, which does not directly represent noradrenaline release, but reflects release minus clearance, has been termed delta[NA]CF. The effects of a number of pharmacological agents on the EJCs were examined both at 0.1 and 2 Hz, and the effects on the EJC response to 100 pulses at 2 Hz compared with that on the delta[NA]CF response. Clonidine and xylazine were used as alpha 2-agonists, yohimbine and idazoxan as alpha 2-antagonists and desipramine and cocaine as blockers of noradrenaline reuptake. Most of these agents had unwanted side effects, especially at higher concentrations. However, clonidine and xylazine depressed at lower concentrations the EJC and delta[NA]CF responses to about the same extent; these effects were partially or completely reversed by yohimbine. Yohimbine or idazoxan did not affect the EJCs at 0.1 Hz but enhanced the EJC and delta[NA]CF responses to 100 pulses at 2 Hz to the same extent. All effects of desipramine (1 microM) seemed explainable as a result of block of noradrenaline reuptake, while cocaine (10 microM) in addition exerted an 'unspecific' depressant (probably local anesthetic) effect. Under control conditions, both agents depressed the EJC but dramatically enhanced the delta[NA]CF response to 100 pulses at 2 Hz. Addition of yohimbine prevented the depressant effect of desipramine on the EJCs completely and reduced that of cocaine, but increased their effects on the delta[NA]CF response. These results are compatible with the view that ATP and noradrenaline are released in parallel from the sympathetic nerve terminals of this tissue. The different, and under some conditions even opposite, effects of desipramine or cocaine on the EJC and delta[NA]CF responses are explainable in terms of the known post-secretory effects of these agents.

Adenosine Triphosphate↗
PubMed1991

Electrochemical and electrophysiological analysis of the effects of SK&F 104078 on prejunctional alpha 2-adrenoceptors.

SK&F 104078 is proposed to be a selective postjunctional alpha 2-adrenoceptor antagonist. We examined its effects on the electrically evoked release of endogenous noradrenaline (NA) from the rat tail artery and of ATP from the mouse vas deferens, as determined electrochemically or by extracellular recording, respectively. The alpha 2-adrenoceptor antagonist yohimbine (0.1 and 1 microM) increased NA release at both 2 and 20 Hz; the effect of yohimbine was further enhanced by the NA uptake blocker cocaine. SK&F 104078 (0.01-1 microM) did not change NA release at 2 or 20 Hz in the absence or presence of cocaine. NA release at 2 Hz was dose dependently depressed by the alpha 2-adrenoceptor agonist xylazine, an effect reversed by yohimbine (1 microM) but unaffected by SK&F 104078 (0.1 and 1 microM). Similarly, the inhibitory effect of xylazine on ATP release at 0.1 Hz was not influenced by SK&F 104078 (1 microM) but partially reversed by yohimbine (1 microM). The results show (i) that prejunctional alpha 2-adrenoceptors mediate autoinhibition of the release of endogenous NA and ATP from sympathetic nerves in the rat tail artery and in the mouse vas deferens, respectively, and (ii) that SK&F 104078 does not block these receptors in the concentration range 0.01-1 microM.

Adenosine Triphosphate↗
PubMed1991

A calcium-dependent component of the action potential in sympathetic nerve terminals in rat tail artery.

A pharmacological approach was employed in order to visualize a Ca2(+)-dependent component of the extracellularly recorded nerve terminal impulse in the secretory regions of the sympathetic postganglionic nerves in the rat tail artery. Application of potassium-channel-blocking agents within the recording electrode caused the nerve terminal impulse to acquire a delayed negative deflection, which we have termed the late negative component (LNC) of the nerve terminal impulse. The time course and the latency of the LNC differed from that of the postjunctional transmitter-induced excitatory junction current, and the LNC persisted when the excitatory junction current was blocked by adenosine [alpha,beta-methylene]triphosphate, and was resistant to the alpha 1-antagonist prazosin and the alpha 2-antagonist yohimbine. Probably, therefore, the LNC was exclusively prejunctional in origin. For the following reasons it seems likely that the LNC, at least in part, was caused by influx of Ca2+ into the secretory regions of these nerves: (a) the LNC occurred only when potassium-blocking agents were present within the recording electrode; (b) the LNC amplitude increased with the Ca2+ concentration inside the recording electrode and was reduced by the removal of Ca2+; (c) the LNC was enhanced by replacing Ca2+ in the medium inside the recording electrode with Ba2+; (d) the LNC was depressed by the inorganic Ca2(+)-channel blocker cadmium or the Ca2(+)-channel-blocking peptide omega-conotoxin added within the recording electrode only, or by addition of cadmium or cobalt (but not the organic Ca2(+)-channel blocker nifedipine) inside and outside the recording electrode.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

K+ and Ca2+ channel blockers may enhance or depress sympathetic transmitter release via a Ca(2+)-dependent mechanism "upstream" of the release site.

Extracellular recording of the pre- and postjunctional electrical activity in guinea-pig or mouse vas deferens or rat tail artery was employed to study the mechanisms by which the K+ channel blockers, tetraethylammonium and 4-aminopyridine and the Ca2+ channel blockers, Cd2+, Mn2+ or nifedipine influence the nerve stimulation-induced release of adenosine 5'-triphosphate as a sympathetic co-transmitter. The K+ and Ca2+ channel blocking agents examined had no effect on the spontaneous quantal release of adenosine 5'-triphosphate. However, addition of tetraethylammonium and 4-aminopyridine inside the recording electrode broadened the nerve terminal action potential and caused it to become more resistant to local application of tetrodotoxin, and dramatically increased the magnitude and tetrodotoxin resistance of adenosine 5'-triphosphate release within the patch. Surprisingly, tetraethylammonium and 4-aminopyridine were equally effective when added outside the recording electrode; now they did not increase the duration of the nerve terminal action potential inside the patch but increased its resistance to locally applied tetrodotoxin and dramatically increased the magnitude as well as the tetrodotoxin resistance of adenosine 5'-triphosphate release from sites inside the patch. Both tetraethylammonium and 4-aminopyridine contributed to these effects, with a strong potentiating interaction. Nifedipine was without effect, but application of 1-100 microM Cd2+ or 1-5 mM Mn2+ either inside or outside the recording electrode blocked adenosine 5'-triphosphate release inside the patch. The results indicate: (i) that the nerve terminal action potential is generated by activation of voltage-gated, regenerative Na+ channels but also has a small component carried by influx of Ca2+ and that it is "normally" terminated by activation of voltage- as well as Ca(2+)-dependent K+ channels; (ii) that the release probability is tonically depressed by the resting K+ efflux, and promoted by the resting Ca2+ influx, "upstream" of the release sites; and (iii) that the upstream control of the release probability may involve both changes in properties of ionic channels in the nerve terminal membrane, and effects on the cytoskeleton leading to changes in the availability of releasable quanta in varicosities within the patch.

4-Aminopyridine↗
PubMed1990

"Upstream" regulation of the release probability in sympathetic nerve varicosities.

The results appear to support the following tentative working hypothesis. (1) Nerve impulse-induced transmitter release from sympathetic nerve varicosities is monoquantal and highly intermittent (probability range: 0-0.03). (2) Nerve impulses invade varicosities as all-or-none, Na+ channel-dependent action potentials; invasion failure may be rare. (3) The release probability is not controlled by properties (amplitude or duration) of the invading action potential or the resulting Ca2+ current, but by the availability of an as yet unidentified permissive factor. (4) The permissive factor is actively transported intra-axonally, probably in association with organelles (LDVs?). (5) The activation and/or transport of the permissive factor are controlled "upstream" of the varicosity; they depend on Ca2+ influx through channels insensitive to nifedipine (hence, not of L-type) but blocked by Cd2+ and apparently opened by slight depolarization of the resting membrane, in this respect behaving more as T- than N-type channels. (6) A high resting K+ efflux "upstream" of the varicosity restricts the availability of the permissive factor; it is the main mechanism maintaining the (economically necessary) low release probability. (7) Prejunctional agonists do not inhibit transmitter secretion by causing a conduction block or by reducing the action potential-induced Ca2+ influx into the varicosity itself, but by depressing the Ca2(+)-dependent activation and/or transport of the permissive factor; they act at least in part via receptors "upstream" of the varicosity. (8) This hypothesis for regulation of the release probability in sympathetic nerves may apply, at least in part, to other neurons as well.

Animals↗
PubMed1990

On-line electrochemical monitoring of the local noradrenaline release evoked by electrical stimulation of the sympathetic nerves in isolated rat tail artery.

A treated carbon fibre electrode was used to measure by differential normal pulse voltammetry or differential pulse amperometry the release of noradrenaline from the sympathetic nerve terminals innervating the smooth muscle in rat tail artery. On calibration in vitro with exogenous noradrenaline in phosphate-buffered saline solution the electrode recorded an oxidation current at +0.1 V, the oxidation potential of noradrenaline. This signal was proportional to the noradrenaline concentration in the solution. When the electrode was apposed to the wall of the artery there was no oxidation current at +0.1 V under resting conditions, but electrical nerve stimulation for 1-100 s at 1-10 Hz induced a current with a peak at this potential. This signal was suppressed by tetrodotoxin, guanethidine or cadmium, or by omission of calcium; it was strongly enhanced by tetraethylammonium and potentiated by the noradrenaline uptake blockers desipramine or cocaine. The results indicate that the carbon fibre electrode method described here may be used to monitor on-line the nerve stimulation-induced increase in the local noradrenaline concentration at the surface of the muscle layer in a blood vessel such as the rat tail artery.

Animals↗
PubMed1990

Neurotransmitters and pre- and post-junctional receptors involved in the vasoconstrictor response to sympathetic nerve stimulation in rat tail artery.

The study was prompted by the need to re-evaluate, in view of the complexity of the evidence in the literature, the relative roles of different sympathetic transmitters and receptors in the contractile response of the tail artery of adult normotensive rats to electrical field stimulation. By the pharmacological approach employed, noradrenaline and adenosine 5'-triphosphate appeared to contribute to this response; the possible roles of other putative transmitters such as neuropeptide Y could not be examined due to lack of specific antagonists. Noradrenaline, clearly the main mediator, exerted both excitatory and inhibitory effects, acting in part via different receptors depending on the stimulus parameters. Thus, yohimbine and prazosin (alpha 2- and alpha 1-adrenoceptor antagonists, respectively) were about equally effective as inhibitors of the noradrenaline-mediated contractile response to stimulation with short trains and/or at low frequency, but the response caused by long trains and/or high-frequency stimulation was much more strongly inhibited by prazosin than by yohimbine. As expected, yohimbine enhanced the [3H]noradrenaline overflow response to long but not to short stimulus trains, presumably because in the latter case the noradrenaline concentration in the relevant biophase was too low to activate the pre-junctional alpha 2-adrenoceptors. Finally, propranolol, an unselective beta-adrenoceptor antagonist, enhanced the neurogenic contraction, indicating that noradrenaline restricts this response by effects via post-junctional beta-adrenoceptors. Adenosine triphosphate appeared to exert dual, excitatory as well as inhibitory, post-junctional effects. Thus, the P2x-purinoceptor desensitizing agent, alpha, beta-methylene adenosine triphosphate, abolished the initial phase, but enhanced the amplitude of the neurogenic contraction, without affecting the nerve stimulation-induced overflow of [3H]noradrenaline. The results indicate that noradrenaline and adenosine triphosphate, the main mediators of the neurogenic contraction of this preparation, act in a more complex fashion than earlier thought; they argue against a significant direct contribution by other putative transmitters but do not exclude that such agents may act indirectly as modulators of this response.

Adenosine Triphosphate↗
PubMed1990

Presynaptic receptors and modulation of noradrenaline and ATP secretion from sympathetic nerve varicosities.

Our results in the model tissues examined show (1) that alpha 2 agonist(s) depressed the secretion of NA and ATP caused by nerve stimulation at low frequency, (2) that the secretion of both NA and ATP was moderately autoinhibited, under conditions when endogenous NA was shown to accumulate extracellularly, (3) that a K+ channel blocking agent increased much more strongly than alpha 2-adrenoceptors block the secretion of both NA and ATP, and also amplified enormously the NA-mediated neurogenic contraction, (4) that, therefore, a high K+ efflux is likely to be much more important than alpha 2-adrenoceptor-mediated autoinhibition for maintaining a low release probability in sympathetic nerve varicosities, and (5) that the alpha 2-adrenoceptor agonist, clonidine, or the Ca2+ channel blocking agent, Cd2+, inhibited transmitter secretion, at least in part, via targets "upstream" of the varicosity.

Adenosine Triphosphate↗
PubMed1989

Basic features of an extracellular recording method to study secretion of a sympathetic co-transmitter, presumably ATP.

An extracellular recording method is described which permits in suitable model tissues (e.g. guinea-pig or mouse vas deferens) study of the nerve impulse in sympathetic terminals and the release of transmitter from sites inside or outside the recording electrode. Negative- or positive-going potentials were assumed to reflect the excitatory junction current (EJC) caused by transmitter released inside or outside the electrode, respectively, and hence termed 'EJCi' (i for inside) or 'EJCo' (o for outside). The EJCo were shown to be Ca2+-dependent, blocked by addition of tetrodotoxin or guanethidine, resistant to the alpha 1-adrenoceptor blocking agent prazosin but suppressed by desensitization of P2-purinoceptors by alpha,beta-methylene ATP, and hence, presumably, are caused by release of ATP as a sympathetic co-transmitter. The amplitude of the EJCo was voltage-dependent and increased with the length and frequency of stimulus trains within the range of 1-50 shocks at 0.1-2.5 Hz. In conclusion, combined use of EJCi and EJCo provides a useful tool for physiological and pharmacological analysis of pre- and post-junctional events associated with the secretion of a sympathetic co-transmitter, presumably ATP.

Action Potentials↗
PubMed1989

Some pharmacological applications of an extracellular recording method to study secretion of a sympathetic co-transmitter, presumably ATP.

Extracellular recording in guinea-pig or mouse vas deferens or rat tail artery was used to study the effects of some pharmacological agents on the nerve terminal spike (NTS) and the secretion of a sympathetic co-transmitter (presumably ATP), as reflected in the excitatory junction current (EJC). A negative-going EJCi (i for inside) was assumed to reflect release from sites inside, and a positive-going EJCo (o for outside) release from sites outside the recording electrode. Passage into or out of the electrode seemed to be slow. Tetrodotoxin (TTX) in the outer medium blocked the NTS and ECJo as well as EJCi; TTX in the pipette blocked stimulus-evoked but not spontaneous EJCi. The dihydropyridine Ca2+ channel blocking agent, nifedipine, was without effect, but Cd2+ in the external medium blocked EJCo and also, by an effect apparently 'upstream' of varicosities, inhibited EJCi (i.e. release within the patch) but not the NTS. When present in the outer medium the alpha 2-adrenoceptor agonists, clonidine and xylazine, blocked both EJCo and EJCi, but not the NTS. The effects of clonidine were blocked by yohimbine, which in itself increased the EJCo by about 50%. Neuropeptide Y and met-enkephalin in the outer medium blocked EJCo; the effect of met-enkephalin was blocked by naloxone. The K+ channel blocking agents, tetraethylammonium and 4-aminopyridine, inside or outside the electrode, increased dramatically the size of EJCi or EJCo, respectively.

Action Potentials↗