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MeSH: Tachyphylaxis

7 hits in PubMed Filters

Article

Temperature coefficient of membrane currents induced by noxious heat in sensory neurones in the rat

The Journal of physiology. 1999 May 15 ; 517 ( Pt 1) (Pt 1) : 181-92.

J Physiol
ISSN 0022-3751
Source

1. Membrane currents induced by noxious heat (Iheat) were studied in cultured dorsal root ganglion (DRG) neurones from newborn rats using ramps of increasing temperature of superfusing solutions. 2. Iheat was observed in about 70 % of small (< 25 microm) DRG neurones. At -60 mV, Iheat exhibited a threshold at about 43 C and reached its maximum, sometimes exceeding 1 nA, at 52 C (716 +/- 121 pA; n = 39). 3. Iheat exhibited a strong temperature sensitivity (temperature coefficient over a 10 C temperature range (Q10) = 17.8 +/- 2.1, mean +/- s.d., in the range 47-51 C; n = 41), distinguishing it from the currents induced by capsaicin (1 microM), bradykinin (5 microM) and weak acid (pH 6.1 or 6.3), which exhibited Q10 values of 1.6-2.8 over the whole temperature range (23-52 C). Repeated heat ramps resulted in a decrease of the maximum Iheat and the current was evoked at lower temperatures. 4. A single ramp exceeding 57 C resulted in an irreversible change in Iheat. In a subsequent trial, maximum Iheat was decreased to less than 50 %, its threshold was lowered to a temperature just above that in the bath and its maximum Q10 was markedly lower (5.6 +/- 0.8; n = 8). 5. DRG neurones that exhibited Iheat were sensitive to capsaicin. However, four capsaicin-sensitive neurones out of 41 were insensitive to noxious heat. There was no correlation between the amplitude of capsaicin-induced responses and Iheat. 6. In the absence of extracellular Ca2+, Q10 for Iheat was lowered from 25.3 +/- 7.5 to 4. 2 +/- 0.4 (n = 7) in the range 41-50 C. The tachyphylaxis, however, was still observed. 7. A high Q10 of Iheat suggests a profound, rapid and reversible change in a protein structure in the plasma membrane of heat-sensitive nociceptors. It is hypothesized that this protein complex possesses a high net free energy of stabilization (possibly due to ionic bonds) and undergoes disassembly when exposed to noxious heat. The liberated components activate distinct cationic channels to generate Iheat. Their affinity to form the complex at low temperatures irreversibly decreases after one exposure to excessive heat.

MeSH
Bradykinin pharmacology MeSH
Ion Channels metabolism MeSH
Capsaicin pharmacology MeSH
Rats MeSH
Cells, Cultured MeSH
Membrane Potentials drug effects MeSH
Neurons, Afferent drug effects metabolism MeSH
Receptors, Drug metabolism MeSH
Ganglia, Spinal cytology drug effects metabolism MeSH
Tachyphylaxis physiology MeSH
Temperature MeSH
Calcium metabolism MeSH
Hot Temperature * MeSH
Animals MeSH
Check Tag
Rats MeSH
Animals MeSH
Publication type
Journal Article MeSH
Research Support, Non-U.S. Gov't MeSH
Research Support, U.S. Gov't, P.H.S. MeSH
Names of Substances
Bradykinin MeSH
Ion Channels MeSH
Capsaicin MeSH
Receptors, Drug MeSH
Calcium MeSH

Article

Procaine excites nociceptors in cultures from dorsal root ganglion of the rat

Neuroscience letters. 1999 Mar 19 ; 263 (1) : 49-52.

Neurosci Lett
ISSN 0304-3940
Source

Procaine, a classical local anesthetic, produces, at low concentration (2-200 microM), excitation in a distinct population of small sensory neurons isolated from newborn rats (2D) and cultured for 1-5 days. The excitation or inward current (>50 pA) induced by procaine was observed in 59 out of 78 neurons. Nearly all these procaine-sensitive neurons (56 of 59) were also sensitive to capsaicin while 8 procaine-insensitive neurons responded to capsaicin (1 microM). In procaine-sensitive neurons tested for responsiveness to noxious heat, a 10 s temperature ramp from 24 to 48 degrees C induced an inward current of 413 +/- 47 pA (SEM, n = 27) and this current was enhanced, in the presence of procaine, about 3-fold (2.8 +/- 0.4, SEM, n = 27). The responses to procaine were concentration dependent and underwent pronounced tachyphylaxis after repeated applications. The voltage-current relationship exhibited outward rectification and the apparent reversal at 25 +/- 4.2 mV (SEM, n = 9) suggesting that the current is carried by cations including Ca2+. This procaine effect may offer an explanation for toxic consequence of the clinical use of local anesthetics.

MeSH
Anesthetics, Local pharmacology MeSH
Capsaicin pharmacology MeSH
Rats MeSH
Cells, Cultured MeSH
Neurons, Afferent drug effects physiology MeSH
Nociceptors drug effects physiology MeSH
Animals, Newborn MeSH
Procaine pharmacology MeSH
Ganglia, Spinal cytology physiology MeSH
Tachyphylaxis MeSH
Calcium metabolism MeSH
Hot Temperature MeSH
Animals MeSH
Check Tag
Rats MeSH
Animals MeSH
Publication type
Journal Article MeSH
Research Support, Non-U.S. Gov't MeSH
Research Support, U.S. Gov't, P.H.S. MeSH
Names of Substances
Anesthetics, Local MeSH
Capsaicin MeSH
Procaine MeSH
Calcium MeSH

Article

Capsaicin-induced membrane currents in cultured sensory neurons of the rat

Physiological research. 1993 ; 42 (5) : 301-11.

Physiol Res
ISSN 0862-8408
Source

Membrane currents induced by capsaicin (CAPS) in cultured sensory neurons from 1- to 2-day-old rats were studied. Responses to CAPS (10 microM) exceeding 1 nA at -50 mV were found in smaller, usually bipolar or tripolar neurons in which GABA (30 microM) induced small or no response. Large, unipolar neurons, which exhibited large responses to GABA, were completely insensitive to CAPS (10 microM). In contrast to GABA, responses to CAPS exhibited a slow rise and slow decay and a marked tachyphylaxis after repeated CAPS applications at high concentrations which made it difficult to study the concentration-response relationship. In partially run-down neurons, which exhibited quasi stable responses, the slope of the ascending phase was concentration-dependent with an apparent association rate constant K1 9 x 10(4) [M-1s-1]. The time constant of the decay was 3.5 s, and was concentration-independent. However, in 5 neurones the EC50 measured from the first series of CAPS applications at increasing concentrations was 0.31 +/- 0.5 microM with a Hill coefficient 1.66 +/- 0.35. The responses to CAPS reversed at +10.4 +/- 2.5 mV suggesting that the current is carried nonselectively by monovalent cations and Ca2+. The channel conductance of CAPS-gated channels at -50 mV calculated from the mean membrane current and variance of the current noise in outside-out patches or measured directly was 28 pS (n = 5). It is suggested that the CAPS-gated channels are either controlled by receptors with a very high affinity or that the channels are controlled by membrane-bound protein(s) which do not depend in their function on the supply of GTP or other intracellular metabolites.

MeSH
Cell Membrane drug effects physiology MeSH
Time Factors MeSH
Electric Conductivity MeSH
gamma-Aminobutyric Acid pharmacology MeSH
Ion Channels drug effects physiology MeSH
Capsaicin pharmacology MeSH
Rats MeSH
Cells, Cultured MeSH
Mice, Inbred BALB C MeSH
Mice MeSH
Neurons, Afferent drug effects physiology MeSH
Osmolar Concentration MeSH
Rats, Sprague-Dawley MeSH
Tachyphylaxis MeSH
Dose-Response Relationship, Drug MeSH
Animals MeSH
Check Tag
Rats MeSH
Mice MeSH
Animals MeSH
Publication type
Journal Article MeSH
Research Support, Non-U.S. Gov't MeSH
Names of Substances
gamma-Aminobutyric Acid MeSH
Ion Channels MeSH
Capsaicin MeSH

Article

Vasoconstrictor reaction to prostaglandins E1 and E2 in the isolated rat hindlimb mediated through serotonin release

European journal of pharmacology. 1993 Jan 05 ; 230 (1) : 69-76.

Eur J Pharmacol
ISSN 0014-2999
Source

The vasoconstrictor effects of prostaglandins E (PGEs) were studied in the isolated perfused hindlimbs of the rat. Doses of PGE1 in the range of 0.01-10 micrograms caused dose-dependent increases in perfusion pressure with rapid development of tachyphylaxis. The pressure increases were inversely temperature-dependent, being 4.8 +/- 1.2 mm Hg at 37 degrees C and 22.2 +/- 1.8 mm Hg at 27 degrees C. The vasoconstriction was limited to PGE1 and PGE2. Other prostaglandins tested, PGF2 alpha, PGD2, PGA1, 7-oxo-PGI2 and arachidonic acid, were without any effect at 27 degrees C. Increased serotonin concentrations were found in the effluent after the administration of 1 microgram of PGE1. The pressor response to PGE1 was blocked by 5-HT2 antagonists, ketanserin (2 micrograms) and naftidrofuryl (100 micrograms), while the alpha-adrenoceptor antagonist phentolamine (6.7 micrograms) was without effect. Rapid tachyphylaxis of the development of vasoconstriction was observed after the repeated administration of PGE1 and PGE2. PGE1 (1 microgram) induced desensitization with more than 60 min duration. All the findings suggest that serotonin was liberated in the rat hindlimbs by PGEs.