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Electrophysiological subtypes of inhibitory P 1 purinoceptors on myenteric neurones of guinea‐pig small bowel
Author(s) -
Christofi F.L.,
Wood J.D.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17050.x
Subject(s) - hyperpolarization (physics) , ccpa , agonist , cgs 21680 , medicine , endocrinology , membrane potential , chemistry , myenteric plexus , electrophysiology , inhibitory postsynaptic potential , adenosine , pharmacology , biology , receptor , biochemistry , adenosine receptor , stereochemistry , immunohistochemistry , nuclear magnetic resonance spectroscopy
1 Conventional intracellular microelectrode techniques were used to subclassify P 1 purinoceptors linked to reduction of cell input resistance, steady‐state hyperpolarization of the membrane potential, or inhibition of fast e.p.s.ps, in neurones of microdissected myenteric plexus preparations from guinea‐pig ileum. The potencies of P 1 purinoceptor agonists were estimated in neurones that were current clamped to a fixed membrane potential. 2 In AH/Type 2 neurones, the A 2 agonist, CGS 21680, the A 1 agonist, CCPA or the mixed A 1 ‐A 2 agonist, NECA, suppressed excitability by reducing input resistance (40–50% max.) and causing hyperpolarization (20–25 mV max.). CGS 21680 (0.1‐1 μ m ) enhanced the after‐hyperpolarizing potential. 3 From cumulative dose‐response data, the potency order for reducing input resistance was CCPA (IC 50 = 5.1 ± 2.2nM) > > > CGS 21680 (IC 50 = 5.6 ± 2.5 μ m ). This effect was reversed by the A 1 antagonist, CPT (EC50 = 65 ± 11 n m ). 4 In contrast, the potency order for membrane hyperpolarization was CCPA (IC 50 = 61 ± 23 n m ) = CGS 21680 (IC 50 = 290 ± 90 n m ) ≥ NECA (IC 50 = 450 ± 100 n m ). Hyperpolarization elicited by CCPA was sensitive to the A 1 ‐A 2 antagonist, DPSPX. 5 Agonists suppressed fast e.p.s.ps, but not DMPP responses, with an order of CCPA (IC 50 = 8.1 ± 3.0 n m ) > > > CGS 21680 (IC 30 = 10 ± 2.9 μ m ). 6 In conclusion, the excitability of AH/Type 2 neurones is suppressed by activation of high affinity A 1 receptors that may be linked to a cyclic AMP‐dependent pathway, leading to increase in calcium‐dependent potassium conductance and enhancement of the after‐hyperpolarizing potential. Activation of lower affinity non A 1 receptors linked to a cyclic AMP‐independent pathway reduces excitability and leads mainly to a steady‐state hyperpolarization. Adenosine also suppresses nicotinic cholinergic transmission by activating presynaptic high affinity A 1 receptors.